Viruses Flashcards Preview

FDN3 By Nathan and Minnie > Viruses > Flashcards

Flashcards in Viruses Deck (405)
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1
Q

What are the important properties/differentiations of the viral genome?

A
  • RNA or DNA
  • Single-stranded or double stranded
  • Linear or circular
  • Segmented or not
  • If single-stranded
    • Positive sense, negative sense, or ambisense
  • Size (from 3,500 nt to 280 kbp)
2
Q

Viral replication requires factors from which sources?

A

Both the host cell and encoded by the virus

Factors encoded by the virus are typically translated into proteins that are then used in genome replication

(determined by nature of viral genome and where it is delivered to the cell)

3
Q

What do the most successful antiviral drugs target?

A

Enzymes/proteins encoded by the virus

4
Q

What would happen if the cellular processes required for viral replication were inhibited in host cells?

A

Both infected and uninfected would have essential functions shut off (protein synthesis, nucleic acid synthesis)

This would lead to toxicity

5
Q

What dictates the strategy of replication utilized by viral families?

A

Properties of the genome

(Ex: ss(+), ss(-), ds, or retrovirus, shape and segmentation may also play a role)

6
Q

Virus-cell interactions determine…

A
  • Pathology
  • Host response and consequences
  • Viral evasion and host responses
  • Targets for antiviral therapy
7
Q

What makes a cell resistant to viral infection?

A

Lacking receptors for viral entry

8
Q

What makes a cell susceptible to viral infection?

A

The cell is suceptile if the virus can enter and either…

  • Express genes
  • Establish its genome inside cell
9
Q

What are the four general types of viral infection in a susceptible cell?

A
  • Non-permissive for infection
  • Productively infected
  • Abortively infected
  • Latently infected
10
Q

What is a productive viral infection?

A

A full viral replicative cycle occurs and viral progeny are produced

11
Q

What is an abortive viral infection?

A

Viral genes are expressed but infectious progeny do not result.

The host cell probably dies

12
Q

What is a latent viral infection?

A
  • Viral genome is established inside cell
  • Some genes are expressed, but virus does not replicate
  • Cell remains viable, but some functions may be altered
13
Q

What consequence to the host cell is productive viral infection associated with?

A

Cell death

14
Q

What kind of viral infection spreads the virus to target organs, causes disease, and transmits the disease to other?

A

Productive viral infection

15
Q

Productive viral infection is necessary in order for the virus to…

A
  • Generate enough virus to spread to target organs and cause disease
  • Transmit disease to others
16
Q

What are the steps in the productive replicative cycle?

A
  1. Attachment
  2. Penetration
  3. Uncoating and disassembly
  4. Transcription
  5. Translation
  6. Replication
  7. Assembly
  8. Release from cell
17
Q

What occurs in the assembly stage of the viral productive replicative cycle?

A

Virus binds to cell surface through interaction of virion proteins w/ existing cell surface receptor

(Some viruses may recognize more than one receptor, allowing use of different receptors on different cell types or alternate routes of entry into a single cell type)

18
Q

What is required in the penetration stage of the viral productive replicative cycle?

What occurs?

A

Energy-dependent

  • Enveloped viruses
    • Fusion of viron envelope with plasma membrane (some)
    • Endocytosis
    • Fusion with endosome membrane
  • Non-enveloped viruses
    • Translocation of virus/viral genome across plasma membrane (some)
    • Endocytosis
    • Translocation across endosome
19
Q

What is the purpose of the disassembly stage of the viral productive replicative stage?

A

Genome becomes accessible for…

  • Translation, if the viral genome functions first as mRNA
  • Transcription, if the viral genome must first be transcribed into mRNA
  • Genome replication (later)
20
Q

Where do most RNA viruses release their genome during the disassembly stage of the viral productive replicative cycle?

A

Cytoplasm (as ribonucleoprotein)

21
Q

Where do most DNA viruses release their genome during the disassembly stage of the viral productive replicative cycle?

A

Nucleus

(May require microtubules or other molecular motors to translocate nucleocapsid from cell periphery to nuclear core)

22
Q

What is the eclipse/replication stage of the viral productive replicative cycle?

A

Period during which viral nucleic acids and proteins are being synthesized, but infectious virus cannot be detected in the infected cell

23
Q

What occurs during the eclipse/replication stage of the viral productive replicative cycle?

A
  • Transcription of viral mRNA
  • Synthesis of viral proteins
  • Replication of viral genome
24
Q

When does assembly occur in the viral productive replicative cycle?

Where does it occur?

A

When progeny viral genomes and viral structural proteins have accumulated to sufficient levels, assembly of the viral genome can occur

Occurs in cell compartment where genome replication occurred (Nucleus for most DNA viruses, cytoplasm for most RNA viruses)

25
Q

In the viral productive replicative cycle, when are most non-enveloped viruses released from infected cells?

A

When the cell lyses

26
Q

In the viral productive replicative cycle, when are most enveloped viruses released from infected cells?

A
  • When they acquire the envelope by budding through plasma membrane
  • When they acquire an envelope by budding through an internal cell membrane into a secretory compartment and are secreted from the cell
27
Q

In a productive viral infection, why is production of a virus usually incompatible with cell survival?

A
  • Cytotoxic effects of viral products
    • Including those that give the virus a competitive advantage for cellular biosynthetic machinery
  • Induction of innate responses that can result in death of infected cells
  • Sometimes cells continually release viruses in addition to being lysed (Hepatitis B infections)
28
Q

What are some examples of cytotoxic effects of viral products that give the virus a competitive advantage for cellular biosynthetic machinery?

A
  • Poliovirus protease cleaves cell cap-binding protein, inhibiting translation of capped mRNAs (poliovirus is uncapped and efficiently translated due to internal ribosome entry site)
  • Herpesvirus protein shuts down splicing of cell mRNAs (most herpesvirus late mRNAs are unspliced)
29
Q

What are four important characteristics of latent viral infections?

A
  1. No viral genome replication except in concert w/ cell division
  2. Few, if any, viral proteins expressed
    - Those expressed can be non-immunogenic
  3. Compatible with cell survival and normal cell functions (some functions may be altered)
  4. Reservoir for reactivation of infectious virus
30
Q

What are the two types of single stranded viral genomes?

A

Positive sense

Negative sense

31
Q

What is a positive sense single stranded viral RNA?

(How does it interact with the host cell?)

A

ss(+) RNA viruses are in the same sense as human mRNA and can be immediately translated by the host cell

32
Q

What is a negative sense single stranded viral RNA?

(How does complare to the host cell?)

A

ss(-) mRNA is complementary to human mRNA

It must be converted to positive sense RNA by RNA-dependent RNA polymerase (encoded by the viral genome) before translation

33
Q

What converts negative sense single stranded viral RNA to positive sense RNA prior to translation?

A

RNA-dependent RNA polymerase (encoded by the viral genome)

34
Q

Describe the DNA nomenclature for viruses with ssDNA

A

Similar to RNA nomenclature

The template strand for viral mRNA is complementary (-) to the ssDNA

The coding strand is a copy of the ssDNA (+)

35
Q

What are the four characteristics of the genomes of RNA viruses?

A
  • Smaller genome sizes (higher error rate when replicating)
  • Maximum upper size limit
  • Often exist as quasispecies
    • Quasispecies = swarms of viruses of the same species with slightly different genome nucleotide sequence
    • Creates a target for natural selection
  • Segmented genomes
36
Q

What is the relationship between genome size and error rate in replication for viral genomes?

A

Inversely related

(smaller genome associated with higher error rate)

37
Q

What occurs beyond the maximal upper size limit of RNA virus genomes?

A

Replication errors render the virus useless or uncompetitive

38
Q

Which broad group of viruses often exists as quasispecies?

What is a quasispecies?

Why are quasispecies important?

A

RNA viruses

Swarms of viruses of the same species but with slightly different genome nucleoside sequences

Prime target for natural selection

39
Q

What are the advantages of segmented genomes?

A
  • Reduce the chance that an error in a single component of the genome will incapacitate the entire genome
  • Reassortment confers evolutionary advantages
40
Q

Why does reassortment of segmented genomes in RNA viruses confer an evolutionary advantage?

A

Different strains of a virus w/ a segmented genome can shuffle and combine genes and produce progeny viruses that have unique characteristics

41
Q

What is notable about the genomes of DNA viruses?

(In comparison to RNA viruses)

A

Larger genome sizes (high fidelity of replication enzymes)

42
Q

What is the exception to the rule that larger genome sizes of DNA viruses are associated with higher fidelity of replication enzymes?

A

Single stranded DNA viruses (mutation rates can approach those of ssRNA viruses)

43
Q

What are the three uses of analysis of viral nucleic acid sequences (viral genomics)?

A
  • Validates original classification
  • Permits studies of evolutionary relationships
  • Enables rapid classification of newly discovered viruses
44
Q

Give 2 examples of viral proteins mediating attachment during the attachment stage of the viral productive replicative cycle

A
  • Influenze - hemagglutinin
  • HIV - gp120
45
Q

Give 2 examples of viruses utilizing existing cell surface molecules in the attachment stage of the viral productive replicative cycle

A
  • Influenze - sialic acid oligosaccharides
  • HIV - CD4, CXCR4, CCR5
46
Q

What is it called when enveloped viruses enter the host cell by fusion of their viral envelope with the cell membrane in the attachment stage of the viral productive replicative cycle?

A

Receptor-mediated endocytosis

47
Q

What occurs in the replicative cycle of ss(+)RNA viruses such as norovirus?

A
  • ss(+)RNA = mRNA
  • ss(+)RNA is ranslation-competent: the ss(+)RNA is translated into a nonfunctional polyprotein by host ribosomes immediately upon entry into cytoplasm
  • The polyprotein cleaved into smaller functional proteins by viral protease
48
Q

What occurs in the replicative cycle of ss(–)RNA viruses such as influenza virus?

A
  • ss(–)RNA is not equivalent to mRNA
  • Viral RNA-dependent RNA polymerase converts ss(–)RNA to mRNA and genomic ss(+)RNA
  • The ss(+)RNA is transcribed by host cell ribosomes in the cytoplasm into a nonfunctional polyprotein
  • The polyprotein is cleaved into smaller proteins by viral protease
49
Q

What do ss(–)RNA viruses use to convert ss(–)RNA to mRNA and genomic ss(+)RNA?

A

Viral RNA-dependent RNA polymerase

50
Q

In the replication cycle of a DNA virus, what do late mRNAs typically encode?

A

Structural proteins

51
Q

In the replication cycle of a DNA virus, what do early mRNAs typically encode?

A

Regulatory proteins and proteins important for DNA replication

52
Q

What occurs in the replicative cycle of DNA viruses such as adenoviruses and herpesviruses?

A
  • Replicate in the nucleus (expect poxviruses)
  • DNA -> mRNA
  • Early mRNA: regulatory proteins, proteins important for DNA replication
  • Late mRNA: structural proteins
53
Q

What occurs in the replicative cycle of retroviruses such as HIV?

A
  • ss(+)RNA does not turn into mRNA
  • The virus utilizes viral RNA-dependent DNA polymerase (reverse transcriptase) to convert the ss(+)RNA to dsDNA
  • The dsDNA is integrated into host cell genome (provirus)
  • Transcription is regulated by the host cell
54
Q

What do retroviruses use to convert ss(+)RNA to dsDNA?

A

Viral RNA-dependent DNA polymerase (reverse transcriptase)

55
Q

What are the cellular consequences of viral infection?

A
  • Numerous cellular processes are compromised
    • Nucleic acid and protein synthesis
    • Maintenance of cytoskeletal architecture
    • Preservation of membrane integrity
  • Induction of apoptosis
    • But many RNA viruses encode proteins that block apoptosis
56
Q

What is the fate of the host cell after viral infection?

A

Virus replication usually results in cell death through direct cytotoxic effects of viral products or innate and adaptive host response

57
Q

Viral replication is compatible with cell survival in absence of adaptive responses for __________ and _________

A

Viral replication is compatible with cell survival in absence of adaptive responses for retroviruses (such as HIV) and hepadnaviruses (such as HBV)

58
Q

What are the four possible clinical consequences of viral infection?

A
  • Inapparent infection: acute or persistent without symptoms (JC virus)
  • Illness to infection: rapid viral multiplication with extensive cell death (Ebolavirus)
  • Illness due to persistent infection: chronic tissue damage (Hep C)
  • Cancer: cells become transformed into rapidly dividing cancer cells (HPV)
59
Q

What is the main purpose of early viral gene expression?

A

Take over host cell machinery

60
Q

What is the most important determinant of the type of cells viruses infect?

A

Surface glycoprotein

(Must have cell surface receptors for the virus)

61
Q

What is episomal latency?

A

Extrachromosomal viral genes floating in the cytoplasm or nucleus

Herpesviruses (HSV, EBV, VZV, CMV)

62
Q

Which family of viruses exhibits episomal latency?

A

Herpesviruses (HSV, EBV, VZV, CMV)

63
Q

What is proviral latency?

A

Viral genome integrated into DNA of host cell (provirus)

Ex: HIV

64
Q

Which virus exhibits proviral latency?

A

HIV

65
Q

What are the four general characteristics of most DNA viruses?

A
  • dsDNA
  • Linear
  • Icosahedral
  • Replicate in the nucleus
66
Q

What are the four general characteristics of most RNA viruses?

A
  • ssRNA
  • Replicate in cytoplasm
  • Smaller genome
  • Haploid
67
Q
  • An epidemic of gastroenteritis is traced to a malfunction at a local water treatment plant. A viral pathogen is identified. What can you likely predict about this virus?
A

It is likely a non-enveloped virus

68
Q

What does enveloped and non-enveloped mean?

A

Enveloped indicates an outer layer composed of a lipid bilayer and proteins derived from the host cell outer membrane or internal membranes and includes some glycoproteins

Non-enveloped means the outer surface of the virus is composed of a viral capsid

69
Q

What is the utility of a viral envelope?

A

The envelope may help viruses bind to host cells and avoid the host immune response

70
Q

What is generally true about the survival of enveloped viruses?

A

The lipid bilayer of an enveloped virus is relatively sensitive to dessication, heat, and detergents, so these viruses are easier to sterilize than non-enveloped viruses, have limited survival outside host environments, and typically must transfer directly from host to host

71
Q

What is generally true about the survival of noneveloped viruses?

A

Nonenveloped viruses are resistant to heat, dessication, and survive well in the environment

72
Q

What are the possible consequences to the cell of viral infections?

A

Usually cell death, sometimes cell survival and either abortive, chronic, or latent infection

73
Q

What is the most common viral infective agent in humans?

A

Rhinovirus

74
Q

Human rhinovirus is a [family, genetic material/sense, shape, portion of virus]

A

Human rhinovirus is a picornavirus that has (+)ssRNA and an icosahedral capsid

75
Q

How is rhinovirus transmitted?

A
  • Aerosols of respiratory droplets and from fomites (contaminated surfaces) including direct person-to-person contact
76
Q

What is notable about the incubation period of rhinovirus?

A

Short incubation period (1-4 days)

77
Q

The onset of infection by rhinovirus is [speed]

A

The onset of infection by rhinovirus is rapid

78
Q

How does rhinovirus cause rapid onset of infection?

A
  • Rhinovirus adheres to surface receptors within 15 minutes of entering respiratory tract
  • Binds to ICAM-1 receptors on respiratory epithelial cells -> infected cells release cytokines and chemokines -> activate inflammatory mediators -> upper respiratory epithelial cell lysis
79
Q

What is the optimal temperature for replication of rhinovirus?

Where is this temperature found?

A

32oC

Nose and large airways

80
Q

Why does rhinovirus rarely cause lower respiratory tract disease?

A

Rhinovirus replicates poorly at 37oC

(prefers lower temperature found in nose and large airways)

81
Q

How many serotypes of rhinovirus are there?

What is notable about the serotypes of rhinovirus?

A

150 serotypes

Little or no serologic cross-reactivity among different serotypes

82
Q

How does the host respond to rhinovirus?

A

Antibody response to exterior epitopes of VP1-VP3

83
Q

Which part of rhinovirus is highly conserved?

Why is this potentially useful?

A

VP4 protein

Potential vaccine target

84
Q

Human Metapneumovirus is [family, genetic material/sense]

A

Human Metapneumovirus is a member of the pneumoviridae family and uses (–)ssRNA

85
Q

Human metapneumovirus may be the _____ most common cause of lower respiratory tract infection in young children (after RSV) and causes a _____ severe disease than RSV

A

Human metapneumovirus may be the second most common cause of lower respiratory tract infection in young children (after RSV) and causes a less severe disease than RSV

86
Q

How is human metapneumovirus diagnosed?

A

RT-PCR

87
Q

What is the treatment for human metapneumovirus?

What is the vaccine for human metapneumovirus?

A

There is no treatment and no vaccine for human metapneumovirus

88
Q

Human coronavirus is [envelope status, genetic material/sense, shape, structure]

A

Human coronavirus is an enveloped (+)ssRNA virus that has a helical nucleocapsid

89
Q

What illnesses does human coronavirus cause?

A

Common cold, bronchitis, pneumonia

90
Q

What are the novel coronaviruses?

A

SARS-CoV and MERS-CoV

91
Q

Human parainfluenza virus is a [family, genetic material/sense]

A

Human parainfluenza virus is a paramyxovirus that has (–)ssRNA

92
Q

What are the subtypes of human parainfluenza virus?

A
  • PIV-1: croup
  • PIV-2: croup
  • PIV-3L bronchiolitis and pneumonia especially in young kids
  • PIV-4: asymptomatic/mild infection
93
Q

How is human parainfluenza virus spread?

A

Person-to-person by contact with infected secretions through respiratory droplets or contaminated surfaces or objects

94
Q

What is the principal host defense against human parainfluenza virus?

A

Humoral immunity

95
Q

How is human parainfluenza virus diagnosed?

A

PCR

96
Q

Who is the mortality risk from human parainfluenza virus limited to?

A
  • Very young children
  • Elderly
  • Immunocompromised
97
Q

Human adenovirus is [envelope status, genetic material/sense]

A

Human adenovirus is a nonenveloped dsDNA virus

98
Q

What allows prolonged survival of human adenovirus outside the body?

A

Human adenovirus is unusually stable to chemical or physical agents and adverse pH conditions

99
Q

What illnesses does human adenovirus cause?

A

URI, pneumonia, conjunctivitis, tonsilitis, croup, gastroenteritis, cystitis, meningitis, encephalitis

100
Q

What is the treatment for human adenovirus?

What is the vaccine for human adenovirus?

A

Treatment (cidofovir, brincidofovir) of limited efficacy

No vaccine

101
Q

Measles virus is a [family, genetic material/sense, size, number of genes encoded]

A

Measles virus is a paramyxovirus that has (-)ssRNA, is 15-19kb, and encodes 6-10 genes

102
Q

How is measles virus spread?

A

Respiratory droplets

103
Q

What is about notable the spread of measles virus?

A

Measles virus is extremely contagious

104
Q

What are the symptoms of measles virus?

A
  • Fever
  • Cough
  • Coryza
  • Conjunctivitis
  • Koplick’s spots
  • Morbilliform rash
105
Q

Describe the progression of the rash caused by measles virus

A

Rash appears several days after fever

Appears first on the head then moves across the body

106
Q

What virus causes Koplick’s spots?

What are Koplick’s spots?

A

Measles virus

Red cheek with white upper fleck inside the cheek opposite the first upper molar (buccal mucosa)

107
Q

What are the three c’s of measles virus infection?

A
  • Cough
  • Coryza
  • Conjunctivitis
108
Q

Complications of measles are common and most severe in ____. They include ___, ____, ____, and _____

A

Complications with measles are common and most severe in adults

They include diarrhea, pneumonia, encephalitis (SSPE: subacute sclerosing panencephalitis), and corneal ulceration leading to corneal ulceration and blindness

109
Q

What is the antiviral treatment for measles virus?

A

No antiviral treatment for measles virus

110
Q

Measles is a leading cause of death among _____

A

Measles is a leading cause of death among young children

111
Q

Human mumps virus is a [family]

A

Human mumps virus is a paramyxovirus

112
Q

What is the clinical presentation of human mumps virus?

A

Human mumps virus presents with parotitis, orchitis, meningitis/encephalitis (rare)

113
Q

How is human mumps virus treated?

A

No antiviral treatment for human mumps virus

114
Q

How is human mumps virus diagnosed?

A
  • Viral culture
  • RT-PCR
  • Serology (positive IgM ELISE or 4-fold rise in IgG)
115
Q

Rubella is [family, genetic material/sense, envelope status, shape]

A

Rubella is a togavirus that has (+)ssRNA and an enveloped icosahedral capsid

116
Q

What is the clinical presentation of rubella?

A
  • Usually mild and subclinical
  • Low grade fever
  • Rash appearing first on face then moving across body
  • Congenital rubella syndrome in neonates (cardiac, cerebral, ophthalmic, auditory defects)
117
Q

Does rubella still exist in the U.S.?

A

No, rubella was eliminated from the U.S. in 2004

118
Q

What is the treatment for rubella?

A

No antiviral treatment for rubella

119
Q

Why is rhinovirus an uncommon cause of severe pneumonia?

A

Rhinovirus replicates poorly at core body temperatures

120
Q

A 28 year old male visiting from Switzerland presents with fever, rash, and small white spots on an erythematous background on his buccal mucosa. What diagnosis would you suspect?

A

Measles

121
Q

A 25 year old pregnant woman presents with fever and joint pains. Serum parvovirus PCR is positive. What complication should she be monitored for?

A

Hydrops fetalis

122
Q

A 6 week old presents with fever, cough, and wheezing. The baby’s mother reports baby is feeding poorly and seems to stop breathing at times.

What is the most likely cause of this illness?

What test can confirm the diagnosis?

What treatment is indicated?

A

RSV (most common cause of lower respiratory tract in children <1 years of age)

RT-PCR on respiratory secretions (rapid antigen tests are a reasonable alternative but false negative test results may occur)

Therapy is primarily supportive

123
Q

Compare the sizes of DNA and RNA viral genomes

A

RNA viruses are usually smaller

DNA viruses are usually larger

124
Q

How are enveloped viruses typically transmitted?

A

Respiratory, parenteral, sexual routes

125
Q

How are non-enveloped viruses typically transmitted?

A

Fecal-oral route

Viruses that can be transmitted through contaminated water are typically non-enveloped

126
Q

Virus X can survive for up to 2 days on plastic or metal surfaces;

Based on this description, do you think virus X is enveloped or non-enveloped?

A

Non-enveloped

Non-enveloped viruses are more resistant to environmental dessication (like what would occur after 2 days on a plastic surface)

127
Q

List the 5 major types of viruses

A
  • Orthomyxovirus
  • Picornavirus
  • Hepadnavirus
  • Poxvirus
  • Retrovirus
128
Q

Describe the capsid and envelope of:

Orthomyxovirus

A

Helical capsic

Enveloped

129
Q

Describe the capsid and envelope of:

Picornavirus

A

Icosahedral capsid

Non-enveloped

(also small)

130
Q

Describe the capsid and envelope of:

Hepadnavirus

A

Helical (spheres and filaments)

Enveloped

131
Q

Describe the capsid and envelope of:

Poxvirus

A

Complex capsid (brick-shaped)

Enveloped

132
Q

Describe the capsid and envelope of:

Retroviruses

A

Icosahedral

Enveloped

133
Q

What advantages and disadvantages do envelopes confer to virons?

A
  • Advantages
    • Greater ability to evade the host immune system
    • Can change quickly to evade the host immune system
  • Disadvantages
    • Susceptible to dessication in the environment
    • Typically must be transmitted via direct contace
134
Q

Suppose you know that a virus has helical symmetry

What is the likely makeup of the viral genome?

A

ssRNA

135
Q

In a helical capsid, what determines the pitch, diameter, and rigidity of the helix?

What determines length?

A

Sizes of protein subunits and subunit interactions determine the pitch, diameter, and rigidity of the helix

Size of the viral RNA determines the length

136
Q

What are the 3 major types of viral structures?

A

Icosahedral (nearly spherical)

Helical

Complex

137
Q

What are the 3 major types of viral structures?

A

Icosahedral (nearly spherical)

Helical

Complex

138
Q

Describe antigenic drift

A
  • Minor changes due to single mutations
  • Occurs in influenza A and influenza B
  • Causes epidemics
  • Associated with seasonal influenza
139
Q

Describe antigenic shift

A
  • Major changes due to gene re-assortment
  • Only occurs in influenza A
  • Creates new H and/or N combinations
  • Causes pandemics
    • Ex: H1N1 = re-assortment of 5 different flu viruses, incuding, human, avian, and swine
140
Q

Describe Mumps

  • Type of virus:
  • Envelope:
  • Nucleic acid:
A

Mumps

  • Type of virus: Paramyxovirus (close relative of measles
  • Envelope: Enveloped
  • Nucleic acid: ss(-)RNA
141
Q

Describe Measles

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Measles

  • Type of virus: Paramyxovirus
  • Capsid: Helical
  • Envelope: Enveloped
  • Nucleic acid: ss(-)RNA
142
Q

Describe Parvovirus B19

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Describe Parvovirus B19

  • Type of virus: Parvoviridae
  • Capsid: Icosahedral
  • Envelope: Non-enveloped
  • Nucleic acid: ssDNA
143
Q

Describe Influenza Virus

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Influenza Virus

  • Type of virus: Orthomyxovirus
  • Capsid: Helical nucleocapsid
  • Envelope: Enveloped
  • Nucleic acid: (-)ssRNA (segmented)
144
Q

Describe Adenovirus

  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Adenovirus

  • Capsid: Icosahedral
  • Envelope: Non-enveloped
  • Nucleic acid: dsDNA
145
Q

Describe Coronavirus (CoV or HCoV)

  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Coronavirus (CoV or HCoV)

  • Capsid: Helical
  • Envelope: Enveloped
  • Nucleic acid: ss(+)RNA
146
Q

Describe Human Metapneumovirus (hMPV)

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Human Metapneumovirus (hMPV)

  • Type of virus: Pneumoviridae
  • Capsid: Helical
  • Envelope: Enveloped
  • Nucleic acid: ss(-)RNA
147
Q

Describe Respiratory Syncytial Virus (HRSV)

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Respiratory Syncytial Virus (HRSV)

  • Type of virus: Paramyxovirus
  • Capsid: Helical
  • Envelope: Enveloped
  • Nucleic acid: ss(-)RNA
148
Q

Describe Parainfluenza Virus (PIV or HPIV)

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Paranfluenza Virus

  • Type of virus: Paramyxovirus
  • Capsid: Helical
  • Envelope: Enveloped
  • Nucleic acid: ss(-)RNA
149
Q

Describe Rhinovirus (HRV)

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Rhinovirus

  • Type of virus: Picornavirus
  • Capsid: Icosahedral
  • Envelope: Non-enveloped
  • Nucleic acid: ss(+)RNA
150
Q

Describe Influenza Virus

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Influenza Virus

  • Type of virus: orthomyxovirus
  • Capsid: Helical tube
  • Envelope: Enveloped
  • Nucleic acid: ss(-)RNA; segmented
151
Q

What are the 5 major targets for antiviral therapy?

A
  1. Entry
  2. Replication
  3. Proviral integration into the host cell dsDNA
  4. Polyprotein processing
  5. Release
152
Q

Describe Rubella

  • Type of virus:
  • Capsid:
  • Envelope:
  • Nucleic acid:
A

Rubella

  • Type of virus: Togavirus
  • Capsid: Icosahedral
  • Envelope: Enveloped
  • Nucleic acid: ss(+)RNA
153
Q

In general, DNA viruses are…

  • Single or double stranded?
  • Circular or linear?
  • Icosahedral or helical?
  • Replicated in…?
A

In general, DNA viruses are…

  • dsDNA
  • Linear
  • Icosahedral
  • Replicated in the nucleus
154
Q

Which virus is the exception to the rule “All DNA viruses are double stranded?”

A

Parvovirus

(ssDNA)

155
Q

Which viruses are the exceptions to the rule “All DNA viruses are linear”

A

Human Papillomavirus (HPV)

Polyomavirus

Hepatitis B Virus (HBV)

156
Q

Which virus is the exception to the rule “All DNA viruses are icosahedral?”

A

Poxvirus

157
Q

Which virus is the exception to the rule “All DNA viruses are replicated in the nucleus?”

A

Poxvirus

158
Q

Which influenza virus (A or B) has greater diversity?
Why?

A

Influenza A

  • Influenza A has many subtypes defined by hemagglutinin (HA) and Neuraminidase (NA)
    • There are 18 HAs and 11 NAs
  • The viral RNA-Dependent RNA Polymerase lacks proofreading
    • Subject to mutation and therefore evolution
  • 8 gene segments encode 10 viral proteins
    • Segments are subject to reassortment
159
Q

Which influenza virus is associated with pandemics?

Why?

A

Influenza A

  • Undergoes re-assortment, often of human and avian influenza
    • Other types alos possible
  • This cause a virus that…
    • The vast majority of the world has no immunity to
    • Has a reservoir in non-human hosts in which antigenic variation can occur
160
Q

Why is influenza B associated with epidemics but not pandemics?

A

Influenza B has no subtype variation; it cannot undergo re-assortment that would cause vastly different phenotypes

  • Influenza B does not undergo antigenic shift
  • Influenza B does undergo antigenic drift
    • These small changes are implicated in the different strains of seasonal flu that are seen every year
    • These are epidemics
161
Q

Describe the clinical manifestations of influenza

A
  • Fever
  • Chills
  • Cough
  • Nasal congestion
  • Myalgia
  • Headache
162
Q

How is influenza diagnosed?

A

Rapid antigen test

or

PCR

163
Q

What are the limitations of the flu vaccine?

A
  • Long production time
  • Limited capacity
  • Moderate efficacy in the elderly and immunocompromised
  • May mutate in vaccine production
  • No cross-reactivity
164
Q

How is influenza virus spread?

A

Respiratory droplets and fomites

  • Fomites can survive…
    • 5 minutes on skin
    • 15 minutes on tissue paper
    • 1-2 days on plastic or metal
165
Q

How is flu treated?

A

Antiviral therapy

  • Most effective if started within 24 hours of onset
  • Very important for elderly or immunocompromised patients
  • Leading treatment: Oseltamivir (Tamiflu)
    • Neuraminidase inhibitor
    • Works against influenza A and B
  • Alternatives: Zanamivir, Baloxavir
166
Q

What does Oseltamivir treat?

What is the mechanism of action?

A

Oseltamivir = Tamiflu; influenza antiviral

Cleaves terminal sialic acid from sialic acid-containing glycoproteins. This prevents the separtion of the virus from the host cell (cannot spread to other cells)

167
Q

Why are M2 inhibitors an inferior treatment to Oseltamivir in treatment of influenza?

A

M2 inhibitors only treat influenza A

There is widespread resistance ot amantadine and rimantidine, leading M2 inhibitor drugs

168
Q

Which virus is the most common cause of severe respiratory illnesses in newborns?

A

Respiratory Syncytial Virus (HRSV)

169
Q

Describe the clinical presentation of Respiratory Syncytial Virus

A
  • Lower respiratory tract infection
    • Bronchiolitis (2-3% of cases)
      • Hospitalization
    • Pneumonia
    • Tracheobronchitis
    • Croup
  • Repeat infection is common
    • Becomes less severe over time
  • Recurrent wheezing often follows severe infection
170
Q

How is respiratory syncytial virus diagnosed?

A

RT-PCR is preferred

Rapid antigen test also available, but false positives are common

171
Q

Which groups are at highest risk for a severe HRSV infection?

A

HRSV = human respiraotyr syncytial virus

Groups at risk:

  • Premature infants
  • Infants with cardiopulmonary disease
  • Infants on ECMO
  • Immunocompromised individuals
172
Q

What is Palivizumab?

What is it used for?

Who should recieve it?

A
  • Palivizumab (synagis) is a monoclonal antibody directed against respiratory syncytial vurus fusion protein
  • It is used to prevent RSV infection (not to treat)
  • High risk infants should receive palivizumab
    • Premature infants
    • Infants with cardiopulmonary disease (especially those on ECMO)
173
Q

How is respiratory syncytial virus treated?

A

Supportive care

(Nebulized hypertonic saline is sometimes given, but it may not be effective)

174
Q

What is the pathogenesis of Parvovirus B19?

A
  • The virus targets erythrocyte progenitors
  • This prevents the synthesis of new red blood cells
  • The virus is mild or benign in healthy children
    • The 5th diesease (Erythema infectiosum)
    • “Slapped cheek appearance”
    • Quick recovery without complications
  • However, it has more severe effects in anyone with a shorter red blood cell lifespan
    • Aplastic crisis in persons with hemolytic anemia
    • Chronic aplastic anemia in AIDS patients
    • Hydrops fetalis (heart failure) infetuses
175
Q

What is hydrops fetalis?

Who does it affect?

A
  • Hydrops fetalis is heat faliure in a fetus infected by parvovirus B19. It leads to abortion
  • A pregnant woman infected with parvovirus B19 can pass the infection on to her fetus
    • <10% of fetuses with an infected mother get hydrops fetalis
176
Q

Which virus is known to cause an aplastic crisis?

Which groups are most likely to be affected?

A

Parvovirus B19

The virus can cause aplastic crisis in persons with hemolytic anemia

177
Q

Which groups are most likely to suffer from complications associated with parvovirus B19?

A

Parvovirus B19 targets erythrocyte synthesis, so anyone with a shorter than normal red blood cell lifespan is more susceptible to complications.

This includes…

  • Persons with hemolytic anemia (ex: sickle cell)
  • Persons with AIDS
  • Unborn fetuses
178
Q

What is the mechanism of action of parvovirus B19?

A

Parvovirus B19 targets erythrocyte progenitors

  • Capsid proteins target blood group P antigen (aka globoside)
  • This arrests erythroid precursor development
  • The result is the formation of giant, inert pronormoblasts
179
Q

Which complications are associated with parvovirus B19?

Which groups are most likely to be affected?

A
  • Acute symmetric polyarthropathy
    • Higher risk in women
  • Aplastic crisis
    • People wtih hemolytic anemia (ex: sickle cell disease)
  • Chronic Aplastic anemia
    • AIDS patients
  • Hydrops fetalis
    • Fetuses
180
Q

What is aplastic anemia?

A

A condition in which your body does not produce enough new blood cells (red or white)

181
Q

A patient presents with a fever.

You look inside her mouth, and see the following spots across from her 1st molar.

What is your leading diagnosis?

A

Measles

These are Koplick’s spots - they are diagnostic of measles

182
Q

Vitamin A can decrease the mortality of which viral disease by 50%?

A

Measles

183
Q

What are the 7 most common causes of the common cold?

A

RIP-RACH (Basicaly what people sound like with a cold?)

  • Rhinovirus
  • Influenza
  • Parainfluenza
  • Respiratory syncytial virus
  • Adenovirus
  • Coronavirus
  • Human metapneumovirus
184
Q

What would be most concerning about seeing a case of Rubella in your ECMH?

A

Rubella has been eliminated from the United States

A case of rubella in Chicago would be worrisome for an outbreak

185
Q

How are noneveloped viruses typically transmitted?

A

Fecal-oral

186
Q

Which broad class of viruses survive well in the environment?

A

Nonenveloped viruses survive well in the environment

187
Q

Rotavirus has [genetic material, unique feature]

A

Rotavirus has 11 dsRNA segmented

188
Q

What genetic material does rotavirus have?

A

dsRNA

189
Q

What is unique about the dsRNA of rotavirus?

A

11 dsRNA segments

190
Q

Why is rotavirus such a successful enteric pathogen?

A
  • Remarkably stable triple-layered particle (TPL)
  • Resistant to low pH and high concentrations of chlorine
  • Utilizes proteolysis of receptor-binding protein VP4 to infect intestinal villi
  • Outer layer removed after entering cell to allow transcription to occur inside double-layered particle through which ssRNA is extruded to serve as mRNAs for protein expression
191
Q

What is the structure of the triple-layered particle of rotavirus?

A
  • Inner icosahedral capsid of VP2 protein
  • Second icosahedral shell of VP6 protein
  • Outer layer of VP4 and VP7
192
Q

What is rotavirus resistant to?

A
  • Low pH
  • Concentrations of chlorine typically used to treat sewage and drinking water
193
Q

What cell components does rotavirus infect?

A

Intestinal villi

194
Q

How does rotavirus infect intestinal villi?

A

Utilizes proteolysis of receptor-binding protein VP4

195
Q

What occurs after rotavirus enters a cell?

A

Outer layer is removed

196
Q

Where does transcription of rotavirus occur?

A

Inside the double-layered particle

197
Q

What is extruded through channels in the double-layered particle?

A

ssRNA that serves as mRNAs for protein expression

198
Q

What are the steps in the rotavirus replication cycle?

A
  1. Enters cell as triple-layered particle (TPL)
  2. Uncoats to get double-layered particle (DPL)
  3. Transcription of ssRNA inside DPL
  4. Extrusion of single stranded RNA through channels in DPL
  5. Viral replication in the inclusion
  6. Viral particle release through lysis of the cell
199
Q

What is NSP4 of rotavirus part of?

A

Double-layered particle

200
Q

What is NSP4 of rotavirus?

A

Enterotoxin

201
Q

What does NSP4 of rotavirus do?

A

Stimulates anion movement across membranes and promotes diarrhea

202
Q

What is VP7 of rotavirus?

A

A glycoprotein of TLP

203
Q

What is VP4 of rotavirus?

A

A protease-cleaved protein of TLP

204
Q

What do VP7 and VP4 of the TLP define for rotavirus?

A

Virus serotype

205
Q

What are VP7 and VP4 of the TLP of rotavirus targets for?

A

Neutralizing antibodies

206
Q

How do VP7 and VP4 of the TLP of rotavirus allow for genetic diversity?

A

Mutation and gene reassortment of the segmented genome

207
Q

How did increased sophistication in clean water supplies and sewage disposal lead to outbreaks of polio?

A
  1. Resulted in limited contact with polio at an early age
  2. Immunity previously generated from early contact with poliovirus was delayed until a later stage of dvelopment
  3. Massive outbreaks of paralytic polio occurred
208
Q

Poliovirus is a [family, envelope, shape]

A

Poliovirus is a picornavirus with a non-enveloped icosahedral capsid (also an enterovirus)

209
Q

How is poliovirus transmitted?

A

Fecal-oral

210
Q

What does poliovirus bind?

A

CD155 cell surface receptor found in humans and some non-human primates

211
Q

Why can polio be eradicated?

A

Poliovirus has no natural animal reservoir

212
Q

Poliovirus has [genetic material/sense] that serves as ____ and encodes _____

A

Poliovirus has (+)ssRNA that serves as a functional mRNA and encodes a polyprotein

(polyprotein is cleaved by viral protease into functional peptides)

213
Q

How does the poliovirus polyprotein become functional?

A

Viral protease cleaves the polyprotein into functional peptides

214
Q

How long does it take for host cell lysis to occur after poliovirus infection?

A

4-6 hours

(release of 10,000 polio virions - a lot)

215
Q

Where does poliovirus replicate?

A

GI tract

216
Q

What is the distribution in the severity of symptoms in people infected with poliovirus?

A
  • ~95% have transient viremia
  • ~5% have sustained viremia w/ fever, headache, sore throat
  • <1% of cases are neuroinvasive
    • 0.1% of cases cause frank paralysis
217
Q

What causes circulating vaccine-derived poliovirus?

A

Complication of live attenuated poliovirus vaccination (OPV)

218
Q

What are the symptoms of circulating vaccine-derived poliovirus?

A

Acute, flaccid paralysis clinically identical to paralysis secondary to wild-type poliovirus

219
Q

How does circulating vaccine-derived poliovirus occur?

A

Mutations in the OPV strain render it virulent

(can spread to communities)

220
Q

What is postpoliomyelitis syndrome?

What causes it?

A

Late progression of muscle weakness

Caused by physiologic attrition of motor units already less innervated as a result of earlier acute infection

221
Q

Astrovirus is a [family, genetic material/sense, shape, unique appearance]

A

Astrovirus is a member of the Astroviridae family with (+)ssRNA, an icosahedral nonenveloped particle, and a characteristic star-like appearance

222
Q

What is the incubation period of astrovirus?

A

4.5 days

223
Q

Which viruses cause acute flaccid myelitis?

A
  • Poliovirus
  • Non-polio enteroviruses
  • West Nile viruses and related viruses such as Japanese encephalitis virus and Saint Louis encephalitis virus
  • Adenovirus
224
Q

Who does astrovirus primarily affect?

A

Children (5-9% of cases of gastroenteritis in young kids)

225
Q

What is the clinical presentation of acute flaccid myelitis?

A
  • Sudden arm and leg weakness
  • Loss of muscle tone
  • Facial weakness or drooping and difficulty swallowing or speaking
  • Severe cases: paralysis, respiratory failure, even death
226
Q

What are the clinical manifestations of astrovirus?

A
  • Diarrhea, nausea, vomiting (less vomiting than rotavirus or norovirus)
  • Typically not severe (no dehydration)
  • Lasts 3-4 days
227
Q

Hepatitis A Virus is [family, genetic material, envelope/non]

A

Hepatitis A virus is a picornavirus that has ssRNA and is nonenveloped

228
Q

Why can Hepatitis A survive under harsh conditions?

A
  • Resistant to detergent, acid, solvents, drying, high temperatures
  • Can survive in fresh and salt water
229
Q

Why can the Hepatitis A vaccine be given as postexposure prophylaxis?

A

Hepatitis A has a long incubation period (30 days)

230
Q

How can Hepatitis A be prevented?

A

Vaccine (95% protection)

231
Q

What is the relationship between jaundice and age in people infected with Hepatitis A virus?

A

Percentage of people infected with Hepatitis A that have jaundice increases with age

232
Q

What are the complications of Hepatitis A virus?

A
  • Fulminant hepatitis
  • Cholestatic hepatitis
  • Relapsing hepatitis

(no chronic infection)

233
Q

How is Hepatitis A virus infection diagnosed?

A

HAV-specific antibodies

234
Q

Hepatitis E virus has [genetic material/sense, envelope/non, shape]

A

Hepatitis E virus has (+)ssRNA, is nonenveloped, and is icosahedral

235
Q

Describe the important characteristics of Hepatitis E virus

(transmission, incubation, tissues affected, fatility, how to diagnose/treat)

A
  • Fecal-oral transmission
  • Common in places with poor sanitation
  • Long incubation period (40 days)
  • Liver tropism
  • No chronic infection
  • Overall case fatility rate higher than Hep A (especially high in pregnant women, particularly in third trimester)
  • Diagnosed by HEV antibody or HEV RNA
  • Effective vaccine developed but stopped b/c not profitable
236
Q

Which enteric virus generates novel strains by gene segment reassortment?

A

Rotavirus

237
Q

A 5 year old boy is sent home from kindergarten with vomiting and diarrhea. The next day his 3 year old sister develops vomiting and diarrhea. What is the most likely cause of their illness?

A

Norovirus

238
Q

A pregnant woman is planning to travel to Bangladesh. What do you advise her to do?

A
  • Not go
  • Practice strict food and beverage precautions
239
Q
A
240
Q

What polio vaccine is administered in the U.S.?

Why?

A

The enhanced inactivated polio vaccine (IPV)

Unlike the live attenuated OPV, the IPV is not associated with the risk of vaccine-derived poliomyelitis

241
Q

Why are dsRNA viruses so uncommon?

Which enteric virus avoids this? How?

A

Pattern recognition receptors (PRRs) present in the cytoplasm have the capacity to sense the presence of viral nucleic acids, particularly dsRNA, as pathogen-associated molecular patterns (PAMPs)

Rotavirus avoids this by extruding capped ss(+)RNA through channels in the DLP, which serve as mRNAs for protein expression. As a result, double-stranded viral genome segments are kept hidden from the cell’s dsRNA sensors

242
Q

Whart is a hallmark of all herpesvirus infections?

A

Ability of the herpesvirus to establish latent infections during the primary encounter with the host, which may/may not result in clinical disease, and to reactivate to cause secondary disease long after recovery from primary disease

243
Q

During the latent phase of herpesvirus what is true with regards to the immune system?

A

Herpesviruses are invisible to the immune system during the latent phase

244
Q

Why might vaccines against herpesviruses be effective to prevent primary disease but be ineffective at preventing latency?

A

Herpesviruses are antigenically stable

245
Q

During herpesviruses latency, how does the viral genome persist in the cell nucleus?

A

As an autonomous episome

246
Q

During herpesvirus latency, what is not necessary for maintenance of the viral genome?

A

Replication of the viral genome is not necessary for its maintenance (post-mitotic)

(example: neurons infected with HSV)

247
Q

During herpesvirus latency, how are viral genomes partitioned to daughter cell nuclei of dividing host cells?

A

Virus expresses EBNA1, which attaches the episomes to cell chromosomes

(examples: B lymphocytes infected with EBV)

248
Q

Why can viral genes be expressed in latent infections?

A

Viral genes are not cytotoxic and do not provoke cytotoxic immune response

(example: EBNA1 inhibits processing of protein for presentation by MHC molecules)

249
Q

What is acyclovir?

A

A nucleoside analogue used to treat herpesviruses, specifically HSV

250
Q

What are the steps involved in the action of acyclovir to treat herpesviruses?

A
  1. Starts as nucleoside analogue
  2. Phosphorylated into monophosphate form by virally-encoded thymidine kinase (lends specificity to acyclovir’s activity because this does not occur in uninfected cells)
  3. Phosphorylated into active triphosphate form
  4. Inhibits viral DNA polymerase
  5. Leads to chain termination

(has 15% bioavailability)

251
Q

Which herpesvirus is acyclovir primarily used to treat?

A

HSV

(HSV>>VZV>EBV>CMV>HHV-6)

252
Q

What is the interaction between acyclovir and viral thymidine kinase?

A

The viral thymidine kinase phosphorylates acyclovir to the monophosphate form

This does not occur in uninfected cells, so this lends specificity to the actions of acyclovir

253
Q

Why would a clinician prescribe valacyclovir instead of acyclovir?

A

Valocyclovir is a L-valyl ester prodrug of acyclovir (converted via hepatic first pass metabolism) that has greater bioavailability

(Valocyclovir has 54% bioavailability while acyclovir has 15% bioavailability)

254
Q

What does a virus need to do to establish latency?

A

In a latent infection, the full viral genome is retained in the host cell, but its expression is dramatically restricted, such that a few viral antigens and no viral particles are produced

To qualify as latency, this cryptic form of infection must display persistence and reversibility

255
Q

What do all enteric viruses share in common?

A

Non-enveloped viruses transmitted by fecal-oral route

Most are ss(+)RNA viruses (except rotavirus, which is a segmented dsRNA virus)

256
Q

How do (+)ssRNA viruses express proteins?

A

The ss(+)RNA functions as mRNA and upon disassembly in the host cell cytoplasm is immediately translated into a polyprotein which is cleaved into smaller viral proteins by a viral proteins

257
Q

Why has the development of an effective norovirus vaccine been so challenging?

A
  • There is very little protection across the multiple genogroups and genotypes
  • Norovirus demonstrates a high rate of mutation and recombination leading to the emergence of novel strains
258
Q

How do primary and reactivated herpes infections differ in their presentation?

A

Primary infections tend to be more severe, although they generally occur in the same area

259
Q

How is the pathogenesis of herpes zoster different from primary VZV infection?

A

Herpes zoser is reactivation of latent virus in a dorsal root ganglion that spreads along the sensory nerve, causing a rash in a dermatomal distribution along the nerve

Primary varicella zoster virus infection is acquired by inhalation of airborne droplet nuclei, infection of the lung, and dissemination to the skin and other organs via the bloodstream

260
Q

What is the characteristic clinical presentation for herpes simplex virus type 1 encephalitis?

A

Focal encephalitis: fever and focal neurologic deficits, most commonly localized to the frontotemporal region

261
Q

What testing can distinguish acute EBV infection from past EBV infection?

A

Acute EBV infection is often associated with positive heterophile antibody test (monospot), elevated anti-EBV IgM, and a negative anti-EBNA IgG

Development of positive anti-EBNA IgG is correlated with resolution of acute EBV infection

262
Q

What are the clinical manifestations of CMV infections in immunocompetent vs immunocompromised hosts?

A

Immunocompetent hosts present with infectious mononucleosis-like syndrome (heterophile mononucleosis)

Immunocompromised hosts typically present with colitis, hepatitis, and retinitis

263
Q

What illnesses are associated with HHV-6 and HHV-8 infection?

A

HHV-6 is associated with

  • Fever and rash (roseola) in kids
  • Heterophile-negative mononucleosis in an older person
  • Encephalitis, pneumotitis, heptatitis in an immunocompromised person

HHV-8 is associated with

  • Kaposi sarcoma
  • Primary effusion lymphoma
  • Multicentric Castleman disease
264
Q

Which malignancies is HHV-8/KSHV infection associated with?

A
  • Kaposi sarcoma
  • Primary effusion lymphoma
  • Multicentric Castleman disease
265
Q

Which malignancies is EBV infection associated with?

A
  • B and T cell lymphomas
  • Nasopharyngeal carcinoma
  • Leiomyosarcoma
266
Q

What are the causes of heterophile-negative mononucleosis?

A
  • False negative (in which case EBV is the cause)
  • CMV
  • Toxoplasmosis
  • HHV-6
  • HIV
267
Q

Which herpesvirus causes oral hair leukoplakia?

A

EBV

268
Q

What is oral hairy leukoplakia?

A

Non-malignant unchecked lytic replication of EBV

269
Q

Which virus has this characteristic “scalloped” border?

A

Norovirus, of the calicivirus family

270
Q

Which virus is known for its “wheel-like appearance” en electron micrographs?

A

Rotavirus

(wheels rotate)

271
Q

Which virus is known for its characteristic star shape?

A

Astrovirus (HAstV)

275
Q

What are the three major categories of picornaviruses?

A

Hepatitis A

Enteroviruses

Rhinoviruses

276
Q

Describe Norovirus

Type of virus:

Capsid:

Envelope:

Nucleic acid:

A

Norovirus

Type of virus: Calicivirus

Capsid: Icosahedral; “cup-like” scalloped border

Envelope: Non-enveloped

Nucleic acid: (+)ssRNA

277
Q

Which virus is the most common cause of acut gastroenteritis in the USA?

A

Norovirus

278
Q

Which virus its the most common cause of acute gastroenteritis in young children?

A

Rotavirus

(Adults are rarely infected because there is a lot of cross-coverage if you are immune to one serotype)

279
Q

In which settings do outbreaks of norovirus typically occur?

A

Anywhere where people are in close contact; the virus is very contagious

  • Hospitals
  • Schools, childcare centers
  • Nursing homes
  • Restaurants
  • Cruise ships
  • Military
280
Q

How is norovirus typically transmitted?

A

Fecal oral route

Viral particles can be aerosolized by vomiting and toilet flust

Airporn particles can be “ingested” and cause illness

281
Q

Describe the clinical symptoms of norovirus

A

Lots of vomiting, diarrheal gastroenteritis

Symptoms persis for 24-48h after a 2-3 day incubation period

282
Q

Would a vaccine for norovirus be effective?

Why or why not?

A

A vaccine for norovirus would not be effective because…

(Norovirus = No effective vaccine)

  • The virus does not establish a good protective immunity in the host
  • The virus exhibits a high mutation rate
  • Immunity is strain (genotype) specific
    • No cross-protection among genogroups
283
Q

Describe Rotavirus

Type of virus:

Capsid:

Envelope:

Nucleic acid:

A

Rotavirus

Type of virus: Reovirus

Capsid: Icosahedral, triple layered particle

Envelope: Non-enveloped

Nucleic acid: dsRNA

284
Q

Which enterovirus is associated with large outbreaks affecting children and adults in close communities?

A

Norovirus

285
Q

Why is norovirus more likley to affect adults than rotavirus?

A

Norovirus mutates quickly and does not establish a good protective immunity in the host.

  • There is no cross-protection between serogroups
  • Re-infections are possible

Rotavirus establishes immunity in the host. Most poeple get one bout of rotavirus as a child, and then are protected for the rest of their life

  • There is cross-protection between serogroups
  • Re-infection is very rare
286
Q

What determinant of pathogenicity of rotavirus causes symptoms in the host?

Describe its mechanism of action

A

NSP4 is an enterotoxin that causes diarrea

  • Required for the development of the DLP
  • Secreted as a fragment that binds cell receptors
    • Mobilizes intracellular Ca2+
    • Stimulates anion (chloride) movement across membranes
    • Promotes fluid secretion into the intestinal lumen
  • This causes explosive diarrhea

`

287
Q

What characteristics of pathogenicity make rotavirus particularly contagious?

A
  • <100 particles are needed to cause infection
  • Lots of viruses are shed in the stool
    • 2 days before diarrhea begins - 10 days after it ends
  • Spread via contaminated hands and objects
    • Survive for hours on hands, days on objects
288
Q

What are the relevant viral proteins of rotavirus?

A
  • VP2
    • Innermost icosahedral capsid
  • VP3
    • Caps newly synthesized viral (+)ssRNA transcripts
  • VP4
    • Recptor binding protein; enhances infection of villi in the small intestine
    • Used in serotype definition
  • VP6
    • 2nd icosahedral shell (outside of DLP, middle of TLP)
  • VP7
    • Used in serotype definition
  • NSP4
    • Enterotoxin that causes diarrhea
289
Q

Would a vaccine against rotavirus be effective? Why or why not?

A

A vaccine against rotavirus would be effective!

  • Vaccine would protect against many serotypes
    • Cross-protection

(and one does exist!)

290
Q

What are the 3 major causes of acute flaccid paralysis?

A

Poliovirus

Other enteroviruses

West Nile

291
Q

What are the symptoms of acute flaccid myelitis?

A
  • Sudden arm and leg weakness
  • Loss of muscle tone
  • Facial weakness or drooping
  • Difficulty swallowing or speaking
  • Severe: paralysis, respiratory failure, death
292
Q

Which viruses might caue hand, foot, and mouth disease?

A

Coxsackie A

EV-71

293
Q

What are the most common causes of aseptic meningitis?

A

Aseptic = viral (no bacteria in CSF)

  • Enteroviruses
    • Coxsackie A
    • Coxsackie B
    • EV-71
294
Q

List the relevant enteroviruses that we have learned about

A

PREACH-EEN

  • Poliovirus
  • Rotavirus
  • Echo Virus
  • Astrovirus
  • Coxsackie A & B
  • Hepatitis A
  • EV-71
  • EV-D68
  • Norovirus

(You can get enteroviruses in church if somebody is contagious, because you’re all sitting close together)

295
Q

Most enteroviruses are…

Type of virus:

Capsid:

Envelope:

Nucleic acid:

Except…

A

Most enteroviruses are…

Type of virus: Picornaviruses
(norovirus = caliciviridae
rotavirus = reoviridae
astrovirus = astroviridae)

Capsid: Icosahedral

Envelope: Non-enveloped

Nucleic acid: ss(+)RNA
(excpet rotavirus = dsRNA)

296
Q

Describe the possible clinical presentations of coxsackie A

A

Hand foot and mouth disease

Aseptic meningitis

297
Q

Describe the possible clinical presentations of coxsackie B

A
  • Upper respiratory infection
  • Myocarditis/pericarditis/dilated cardiomyopathy
  • Meningitis
  • Pancreatitis
  • Sharp lower chest pain
298
Q

Which enterovirus can cause an infected individual to require a heart transplant?

A

Coxsackie B

It can cause severe heart damage

299
Q

Describe the clinical presentation of echo virus

A

Nonspecific fever, rash

300
Q

Describe the clinical presentation of EV-D68

A

Mild to severe respiratory infection

301
Q

Describe the clinical presentation of EV-71

A

Hand, foot, and mouth disease

Meningoencephalitis

302
Q

Which enteric viruses do not caue gastroenteritis?

A
  • Coxsackie A
  • Coxsackie B
  • Echo virus
  • EV-D68
  • EV-71
303
Q

Which polio vaccine is administerd in the USA?

Why?

A

Enhanced, inactivated polio vaccine

  • Similar to the one created by Salk
  • Lower risk of vaccine-associated poliomyelitis
  • Wil not mutate to a virulent form (chance of this in live, attenuated oral vaccine)
  • Does not shed in feces
    • Will not “immunize” others, but also will not infect them
304
Q

What vaccines are available to prevent polio?

A
  • Enhanced, inactivated polio vaccine (IPV) by Salk
    • Given in the USA
    • Will not mutate to a virulent form
  • Oral polio vaccine (OPV) by Sabin
    • Live, attenuated virus
    • Used in resource-limited countries
    • Small chance of spontaneous mutation to a virulent form
      • CVDPVL circulating, vaccine-derived poliovirus
305
Q

Why are dsRNA viruses uncommon?

A

dsRNA is a PAMP recognized by pattern recognition receptors in our cytoplasm

Rotavirus is able to be a successful pathogen with dsRNA because the TLP/DLP “hide” the dsRNA from the host detection system

306
Q

List the important herpesviruses, grouped by family

A

Alpha herpes viruses

  • HSV-1
  • HSV-2
  • VZV

Beta herpes viruses

  • CMV
  • HHV6
  • HHV7

Gamma herpes viruses

  • EBV
  • HHV8 (KSHV)
307
Q

Describe the characteristics of the alpha-herpes viruses

A
  • Neurotropic
  • Broad host range
    • Can infect adults and children
    • Can infect immune-competent and compromised
  • Highly lytic in cell culture
308
Q

Describe the characteristics of the beta-herpes viruses

A
  • Restricted host range
    • More likely to affect immunocompromised patients
  • Grow more slowly in culture
  • Infected cells have cytomegaly
309
Q

Describe the characteristics of gamma herpes viruses

A
  • Lymphotrophic
  • Can be oncogenic
310
Q

Which herpes viruses can be ocogenic?

A

EBV

HHV8 (KSHV)

311
Q

What is the “hallmark” of herpes viruses?

A

They are forever; They establish latent infections

  • Remain invisible to the host
  • Replicates if/when the host cell DNA does
  • Viral proteins block apoptosis, but do not exert virulence
    • This would give away their hiding spot!
312
Q

What is the prevalence of HSV-1?

A

90% of adults are infected

313
Q

Which herpes virus is associated with oral/labial lesions and can infect a broad host range?

A

HSV-1, also known as herpes labialis

314
Q

What complications can arise from HSV-1?

A
  • Herpetic keratitis
    • Treatable, infectious blindness
  • Encephalitis
    • Fever, focal encephalopathy (CT/MRI will reveal lesions on one side of frontal temporal lobe), personality changes
    • Can be fatal
    • May occur in primary or reactivation infections if the virus travels to the CNS from the dorsal root ganglia
315
Q

A patient presents with a severe headache right side of their head and a fever

Physical exam reveals a tender sore next to and underneath the fingernail of the patient’s right index finger.

The patient reports that they have had similar sores on that finger in the past, but doesn’t think much of it becase it goes away on its own

Is the fingernail significant?
What might be causing these symptoms?

Should the patient be treated?

A

The fingernail is significant!

This sounds like a case of HSV-1; If this is the case, the fingernail could be herpetic whitlow (aka paronychia), and the headache might indicate encephalitis, a rare but serious complication of HSV-1

The diagnosis can be confirmed with a Tzank prep or PCR

The patient should be treated with acyclovir or valacylovir to prevent progression of encephalitis

316
Q

How are HSV viruses diagnosed?

A

Tzank prep (look for multinucleated giant cell) or PCR

317
Q

Describe the common clinical manifestations of HSV-1

A

Primary infection

  • Gingivostomatis
  • Pharyngotonsilitis
  • Complications to post-op course

Reactivation

  • Cold sores outside of the mouth
    • Sores can also appear in other places
    • Ex: finger/fingernail (herpetic whitlow)
  • Bell’s palsy
  • Encephalitis
  • Keratitis
318
Q

How is HSV-1 transmitted?

A

Close person to person contact

  • Exposure to broken skin or mucosa
  • Usually oral, may be genital
319
Q

Where do alpha herpes viruses remain latent?

A

HSV-1, HSV-2, and VZV all reamain latent in the sensory/dorsal root ganglia

(HSV may also be in autonomic ganglia)

320
Q

Which herpes viruses remain dormant in sensory ganglia?

How is this related to their reactivation infections?

A

HSV1, HSV2, VZV; all of the alpha herpesviruses

All three viruses have the ability to cause some kind of neuropathy upon reactivation

  • HSV1 = encephalitis
  • HSV2 = meningitis (although this is usually benign)
  • VZV = shingles; lesion in one dermatome, may lead to paresis, myelopathy, post herpetic neuralgia
321
Q

Which viruses can be treated with acyclovir or valacyclovir?

A

alpha-herpes viruses

  • HSV-1
  • HSV-2
  • VZV
322
Q

Describe the mechanisms of infection and reactivation of HSV

A

Infection

  • HSV replicates in and destroys epithelial cells
  • Enters endings of adjacent neurons
  • Transport through axons to sensory (dorsal root) ganglia
  • Establish latent infection
    • LAT = Latency-associated transcript (the only viral protein expressed)

Reactivation

  • Some stimulus activates the expression of virual genes
  • Production of virus
  • Travel to body surface
  • Lesion forms at or near the site of primary infection
    • Typically mouth for HSV-1, genitalia for HSV-2
323
Q

What is the prevalence of HSV-2?

A

1/5 adults are infected

324
Q

How is HSV-2 transmitted?

A

Close person to person contact

  • Exposure to broken skin or mucosa
  • Usually genital, can be oral
325
Q

Which individuals are at the highest risk for complications from HSV-2 infection?

A

Neonates

(So you would also be concerned if an infected mother contracted a new HSV-2 infection in the first or third trimester)

  • First trimester b/c HSV-2 is a TORCH agent that can cause birth defects
  • Third b/c mother can pass virus to neonate during delivery, resulting in a severe infection with lifelong defects
326
Q

Suppose you have a pregnant patient who contracted HSV-2 about 10 years ago. She is in labor, and you notice a genital lesion as she is getting ready to deliver

Are you worried about transmission of HSV-2 to the neonate? Why or why not?

A

No need to worry!

The mother has likely passed IgG antibodies to the fetus through the placenta during pregnancy.

Therefore, the newborn already has antibodies to HSV-2, and is not at risk for an infection

327
Q

Describe the clinical presentation of HSV-2 in adults

A
  • Genital lesions
  • Mollaret’s meningitis
    • Benign, recurrent lymphocytic meningitis
328
Q

What is the most common primary infection of VZV?

Describe the symptoms

A

Chickenpox

  • Systemic disease
  • Fever, headache, body rash
    • “Dew drop on rose petal”
  • Adults may have complications
    • Pneumonia
    • Encephalitis
329
Q

Describe the patogenesis of a VZV primary infection

A

Inhalation of respiratory droplets

  • Primary viremia (free virus)
    • Replication of virus in spleen or liver
  • Second degree viremia
    • Virus-infected leukocytes cary virus to capillary endothelial cells
    • Virus spreads to epithelium
    • Characteristic lesions on skin and mucosa (resembles HSV lesions, but more widespread)
      • Accompanied by fever, headache
    • Virus seeds neurons and/or other cells in peripheral sensory ganglia
      • Lifelong latent infection
330
Q

How is VZV transmitted?

A

Cutaneous skin legions produce highly infectious virus that are aerosolized

Spread through air and ventilation systems as respiratory droplets

Inhalation by new host

331
Q

What are the risk factors for reactivation of VZV?

A

Reactivation of VZV = Herpes zoster virus = Shingles

Risk factors

  • Waning immunity
    • Old age
    • Immune suppression
    • Sress
332
Q

Describe the pathogenesis of reactivation of VZV

A

Shingles

  • Waning immunity + stimulus to nerves = reactivation
  • Begins as logal, abnormal sensation/tingling/itching
  • Sensation progresses to acute pain
  • Skin lesions erupt in the dermatome of the infected nerve
    • Usually only one dermatome is infected, one additional above or below is possible
    • More than this = disseminated HZV (occurs in immunocompromised patients
  • Resolution: 2-4 weeks later
333
Q

What are the possible complicaitons of herpes zoster virus?

A
  • Zoster opthalmicus
    • Vision loss due to involvement at the first division of the trigeminal nerve
  • Paresis
  • Myelopathy
  • Vasculopathy
  • Post-herpetic neuralgia (PHN)
334
Q

What is post-herpetic neuralgia?

A

Post-herpetic neuralgia = PHN

  • Complication of reactivation of VZV
  • Nerve is inflammed or injured
  • Pain persists after shingles rash has subsided
335
Q

How can VZV be prevented?

A

Primary infection: Chickenpox (Varicella zoster virus)

  • Prevented with live, attenuated vaccine

Reactivation infection: Shingles (Herpes zoster virus)

  • Adults who had chicken pox as children can reieve a recombinant VZV glycoprotein E antigen with adjuvant to prevent reactivation
    • Recommended for adults >50 years old
  • A live, attenuated virus was previously used, but it was not as effective (50%), and it could not be given to immunocompromised patients
336
Q

How can VZV infection be treated?

A

Both chickenpox and shingles can be treated with acyclovir or valacyclovir

Can also use famiciclovir for shingles

337
Q

In the clinic, how would you differentiate between mononucleosis caused by HCMV and mononucleosis caused by EBV?

A

EBV mononucleosis is typically more severe, monospot test will be positive

HCMV mononucleosis may be asymptomatic or subclinical in immune-competent patients, monospot test will be negative

338
Q

Which individuals are most likely to have severe infections and complications from HCMV?

A

Patients who are not fully immune-competent

  • Patients with HIV/AIDS
  • Transplant patients
  • Neonates (congenital CMV infection)
339
Q

How is an HCMV infection treated?

A

Ganciclovir or valganciclovir

340
Q

Describe the presenation of an HCMV infection in an immune-competent patient

A

Primary

  • Asymptomatic or subclinical mononucleosis

Reactivation

  • Mild, general illness
341
Q

Describe the presentation of HCMV in an immunocompromised patient (HIV/AIDS and Transplant)

A

In general: either primary or reactivation infection can cause colitis, hepatitis, and/or retinitis

HIV/AIDS

  • Retinitis/retinopathy
  • Polyradicuolopathy
    • Pain/weakness/loss of sensation
  • Esophagitis
  • Colitis

Transplant patients

  • CMV syndrome
    • Fever, leukopenia, atypical lymphocytosis, hepatosplenomegaly, myalgia, arthralgia
  • Interstitial pneumonitis/pneumonia
  • Colitis
342
Q

Describe the presentation of a congenital HCMV infection

A

Can be acquired intra-natally or perinatally

  • Intranatal = more severe
    • Acquired from non-immune mother
    • Jaundice
    • Hepatosplenomegaly
    • Petechial rash
    • Deafness
    • Neurological effects
      • Microcephaly
      • Motor disability
      • Chorioretinitis
      • Cerebral calcifications
  • Perinatal = more subtle effects on hearing and intelligence
343
Q

Which virus represents the leading causes of congenital mental retardation and hearing loss?

A

HCMV

344
Q

How are beta herpes virues treated?

A

ganciclovir or proganciclovir

345
Q

Describe the clinical presentation of HHV6 in a young child

A

HHV6 = 6th disease = Roseola

  • Typicaly occurs at 6 mo - 2 yo
  • 3-4 days of high fever (>104 F)
    • May cause febrile seizures
  • As fever subsides, body rash that spares the face forms
    • Lacy red rash
  • The illness is self limiting
    • Can be treated with ganciclovir or valganciclovir
346
Q

What is the causative agent of roseola?

Which individuals are most likely to be affected?

A

HHV6; young children (6 mo to 2 yo)

347
Q

Which herpes viruses can be oncogenic?

A

EBV

HHV8 (Kaposi Sarcoma HV)

348
Q

How is EBV transmitted?

A

Oral secretions

EBV = mono = the “kissing disease”

349
Q

What is the site of latency of HCMV?

A

Mononuclear cells, PMNs, and/or vascular endothelial cells

350
Q

What is the site of latency of EBV?

A

B-cells

351
Q

Describe the pathogenesis of EBV

A
  • Transmisison via saliva
  • EBV infects B-cells
  • B-cells express EBV antigens
  • T-cells mount a response, causing a transient, self-limiting, lymphoproliferative syndrome
    • Large cytokine release causes “mono symptoms”
  • Large increase in T-cells
  • The T-cells target and kill infected B-cells that are expressing EBV antigen
  • Resolution of the lymphoproliferative phase occurs when the T-cells have killed off the infected B-cells
  • Some infected B-cells persist becasue they didn’t express EBV antigen!
    • This is where the latent virus lives
352
Q

Describe the symptoms of EBV activation in an immune-competent patient

A
  • Viral replication in B-cells or epithelial cells in the oropharynx leads to shedding of the virus in the saliva
  • This can occur without apparent disease
353
Q

Describe the possible complications of EBV

A

Non-cancer

  • Post-transplant lymphoproliferative disease
  • Primary CNS lymphoma
  • Oral hairy leukoplakia
    • Looks like thrush but doesn’t scrape off
    • Non-malignant

Cancer

  • Burkitt’s lymphoma (non-Hodgkin lymphoma)
  • Hodgkin lymphoma
    • Mixed cellularity, lymphocytes depleted
  • Nasopharyngeal carcinoma
354
Q

Which 3 cancers are associated with EBV?

A
  • Burkitt’s lymphoma (non-Hodgkin lymphoma)
  • Hodgkin lymphoma
    • Mixed cellularity, lymphocytes depleted
  • Nasopharyngeal carcinoma
355
Q

How is EBV diagnosed?

A
  • PCR
  • Heterophile assay aka mononuclear spot test aka “monospot”
    • Human antibodies will agglutinate (clump) sheep or horse blood
      • 70-92% sensitive
      • 96-100% specific
  • Anti-EBNA IgG
    • Negative during active primary infection (IgM will be high at this time)
    • Positive when the primary infection has subsided
356
Q

You suspect your patient has mono, but the monospot has come back negative twice.

What else might be causing the persistent fatigue, fever, and sore throat that this patient is experiencing?

A

HIV

(HIV should be on the differential for anyone with mono-like symptoms who has a negative monospot)

357
Q

Describe the clinical presentation of HHV8 (KSHV)

A

Symptoms only in immunocompromised patients

  • Erythematous, violet lesions on nose an exremeties
  • Mononucleosis

(immune competent patients will be asymptomatic or subclinical)

358
Q

What complications can arise from HHV8/KSHV?

Which patients are most likely to have these complicaitons?

A
  • Kaposi sarcoma
    • an AIDS-defining illness
    • Lesions can be cutaneous and/or visceral
  • Primary effusion lymphoma (B-cell lymphoma)
  • Multi-centric castleman disease
359
Q

How is HHV8 treated?

A

Antivirals are not effective

Treat with…

  • Antiretroviral followed by chemotherapy
360
Q

Describe Herpesviruses

Family:

Capsule:

Envelope:

Nucleic acid:

Size:

A

Herpesviruses

Family: Herpes

Capsule: Icosahedral

Envelope: Enveloped

Nucleic acid: dsDNA

Size: Large! >100,000 base pairs

361
Q

How is EBV treated?

Can it be prevented?

A

Treatment = supportive

No vaccine is available

362
Q

What is the mechanism of action of acyclovir?

A

Acyclovir inhibits viral DNA polymerase, preventing viral genome replication

  • Herpes thymidine kinase phosphorylates acyclovir to acyclovir triphosphate
  • Acyclovir triphosphate competes for endogenous deoxyguanosine triphosphates
  • Bindind acyclovir triphosphate in the growing DNA transcipt is chain-terminating; viral DNA polymerase is inhibited
363
Q

How do primary and reactivated herpes infections differ in their presentation?

A

Usually the primary infection is more severe

364
Q

Do latent viruses always cause recurrent infections?

A

No

VZV will only reactivate once to cause shingles

(but other, such as HSV, cause recurrent reactivaiton infections)

365
Q

Which virus is associated with kaposi sarcoma?

A

HHV8 (aka KSHV, Kaposi Sarcoma Herpes Virus)

366
Q

Describe the clinical presentation of HHV6 in an adult

A

Infectious mononuclosis

(Note: HHV6 causes roseola in young children)

(heterophile/monospot test will be negative)

367
Q

Describe HIV

Family:

Envelope:

Nucleid Acid:

A

HIV

Family: Retrovirus

Envelope: Enveloped

Nucleid Acid: ss(+)RNA

368
Q

How does HIV adhere to and enter host cells?

A

Early virus: Infects macrophages

  • gp120 on the viral envelope binds to host cell CD4
  • CCR5 coreceptor on host macrophage is activated

Later virus: Infects CD4+ helper T-cells

  • gp120 on the viral envelope binds host cell CD4
  • CXCR4 coreceptor on host T-cell is activated
369
Q

Which HIV proteins are important for entry and infection of host cells?

A
  • gp120: Binds to host CD4
  • RT: Reverse transcriptase - turns ss(+)RNA into DNA
  • IN: Integrase - integrates the DNA transcript into the host genome
  • PR: Protease - cleaves viral polyprotein into funcitonal units

Note: Pol is the HIV gene that encodes RT, IN, and PR

370
Q

After entry into a host cell, how does HIV destruction by the host cell?

A

Rev

371
Q

Which subsets of CD4+ T-cells can be infected by HIV infection?

What are the effects of infection of each subset?

A

Effector CD4+ helper T-cells and Memory CD4+ helper T-cells

  • Infection of effector CD4+ helper T-cells
    • Proviral DNA is transcribed
    • Viral proteins are produced
    • The virus spreads
    • These cells are eliminated by the immune system; eventually they will be depleted (without treatment)
  • Infection of memory CD4+ helper T-cells
    • Proviral DNA is not transcribed
    • Viral proteins and antigens are not produced
      • The infection is invisible to the immune system
    • This is why HIV cannot be cured; the virus will persist here silently, spreading to effector cells if necessary
372
Q

What are the goals of HIV treatment?

A
  • Prevent spread of HIV
  • Prevent progression of HIV
    • Maintain leukopoetic stem cells
    • Prevent depletion of CD4+ Helper T-cells
    • This will prevent/slow progression to AIDS

The virus will not be completely eliminated from the host

373
Q

What is the effect of a deletion that eliminates the CCR5 receptor?

A

The person posessing this mutation is immune to HIV infection

374
Q

List the steps in the course of an HIV infection in an untreated individual

A
  • Transmission/incubation
    • 2-3 weeks
  • Primary infection = Acute retroviral syndrome
    • Lasts 2-3 weeks
    • Primary acute mononuclosis or asymptomatic
      • Heterophile/monospot negative
  • Clinical latency
    • Lasts ~8 years
    • No obvious symptoms
    • May be more prone to contracting infections
    • Lots of virions produced, CD4+ T-cells killed, new ones generated
  • Progression to AIDS = CD4+ T-cell count <200/uL or AIDS defining is present
    • Lasts ~1.3 years, ends in death
    • Immune system has lost its ability to replace the CD4+ T-cells that are infected and killed by the virus
375
Q

Desribe the “clinical latency” stage of HIV

A
  • No outward symptoms
  • Individual may get sick more often
    • Community acquired pneumonia
    • Generaly lymphadenopathy
    • Herpes zoster
    • Cervical dysplasia
  • 10^8-10^9 virions are produced each day in effector CD4+ T-cells
    • Spread to infect other effector CD4+ T-cell
    • The immune system is killing the infected cells
    • The virus may be mutating
  • Lymphopoetic system is replacing the lost CD4+ T-cells
    • Gradual decrease in numbers may be happening
    • Will progress to AIDS if CD4+ progenitor cells in bone marrow are lost
376
Q

Describe the clinical presentation of an HIV infection that has progressed to AIDS

A

AIDS = CD4+ T-cell count <200/uL or AIDS-defining malignancyis present

Clinical symptoms

  • Weight loss
  • Unexplained illnesses
  • AIDS-defining illnesses:
    • Kaposi sarcoma
    • B-cell lymphoma
377
Q

A patient in your ECMH presents with pneumonia-like symptoms.

You take a full history, and discover that the patient thinks they had mono ~6 months ago. Physical exam reveals lymphadenopathy

What is the most concerning diagnosis that should be on your differential?

A

HIV

  • Acute retroviral syndrome presents with mononucleosis
  • Patients who are in the “clinical latency” phase often present with lymphadenopathy, community acquired pneumonia, shingles, and/or cervical dysplasia
378
Q

Describe the treatment for HIV

A

Combination of drugs to combat rapid mutation rate

  • 2 nucleoside/nucleotide analogs (inhibit reverse transcriptase)
  • 1 integrase inhibitor and/or 1 protease inhibitor
379
Q

Describe the clinical presentation of dengue fever

A

Classic dengue fever

  • Severe pain (muscle, joint, bone)
  • Nausea/vomiting
  • Rash
  • Conjunctival ingection
  • Leukopenia
  • Thromboytopenia
  • Hemorrhagic manifestation

Hemorrhagic dengue fever

  • Fever
  • Sever thrombocytopenia (<100k)
  • Increased vascular permeability
    • Hemoconcentration
    • Pleural effusion or ascites
380
Q

What is the reservoir of dengue fever?

A

Humans, mosquitos

381
Q

What is an arbovirus?

A

A virus that can be transmitted via insect vector

These viruses have evolved to be able to survive and reproduce in its insect vector

Reservoir for an arbovirus may be human or zoonotic

382
Q

Describe the emergence of West Nile VIrus

A

First case: 1937, Uganda

USA: 1999, NYC

383
Q

How is Dengue fever transmitted?

A

Aedes mosquito

Vertical transmission from mother to fetus is possible

384
Q

Describe the clinical presentation of West Nile Virus

A
  • 1/5 of infected people develop symptoms
    • Flu-like
  • 1% of infected people develop complications
    • Encephalitis (most common)
    • Meningitis
    • Acute flaccid paralysis
385
Q

How is West Nile Virus diagnosed?

A

West Nile Virus IgM in serum or CSF

386
Q

What is th treatment for West Nile Virus?

A

Supportive

387
Q

What is the treatmetn for dengue fever?

A

Supportive

388
Q

List the relevant flaviviruses

A

Dengue fever

West Nile Virus

Zika Virus

389
Q

Describe the clinical presentation of chikungunya virus

A
  • Fever
  • Arthralgias
  • 60% of infected have persistent joint pain for years
390
Q

How is chikungunya virus transmitted?

A

Aedes mosquito

Vertical transmission mother -> fetus

391
Q

List the viruses (discussed in FDN3) that can be transmitted by mosquito.

Identify the type of mosquito

A

Aedes

  • Chikungunya virus
  • Dengue fever
  • Zika Virus

Culex

  • West Nile Virus
392
Q

How is Zika virus transmitted?

A

Aedes mosquito

Sexual transmission

Vertical transmission mother -> fetus

393
Q

Describe the emergence of Zika virus

A

1947: infected rhesus monkey (Uganda)

1947-2007: Not common in humans

2015: Emerged in Brazil, swept through the Americas

394
Q

Describe the clinical presentation of Zika virus

A

Usually mild

  • Symptoms
    • Acute onset
    • Fever
    • Maculopapular rash
    • Arthralgia
    • Conjunctivitis
    • Myalgia
    • Headache
  • Lasts days - 1 week
  • Severe disease is uncommon; case fatality is low
  • Complications are possible
    • Guillan-barre syndrome
    • Infection in pregnancy -> congenital infection
      • Microcephaly
395
Q

Dengue fever, Zika virus, and Chikungunya fever are endemic to similar regions and may present with similar symptoms.

What would you look for to distinguis between them?

A

Look at the most prominent symptom

Dengue: Muscle/bone pain

Chikungunya: Joint pain

Zika: Rash

396
Q

How is Zika virus treated?

A

Supportive

397
Q

Which populations should be most cautious when traveling to areas in which Zika virus is endemic?

A

Pregnant women

398
Q

What complication of Zika virus is most likely to arise in pregnant women?

A

Vertical transmision -> Microcephaly of infant

399
Q

What is the reservoir for West Nile Virus?

A

Birds

400
Q

What is the reservoir for Ebolavirus?

A

Bats, Primates

401
Q

How is Ebola transmitted?

A

Direct contact with infected bodily fluids

402
Q

How is SARS-CoV Transmitted?

A

Bats -> Civets -> Humans

Human - Human

Humans are infected by respiratory droplets

403
Q

How is MERS-CoV transmitted?

A

Bats -> Camels -> Humans

Human - Human

Humans are infected by respiratory droplets

404
Q

Why do SARS-CoV and MERS-CoV have relatively high case fatality rates?

A

Zoonotic viruses like SARS-CoV and MERS-CoV have high case-fatality rates becuase they are new to humans.

The virus hasn’t yet evolved a balance between viral replication and keeping the host alive, resulting in death of the host.

405
Q

Why are some viruses able to be transmitted my mosquitos, while others are not?

A

To be transmitted by mosquitos or other insects, a virus must be able to infect and replicate inside of the mosquito (usually in the midgut)

Not all viruses can do this

406
Q

When is Ebola infectious?

A

From the first sign of illness through 21-41 days after symptoms have resolved

(The virus can persist in semen and conjunctiva for 6-12 months, although it is not known if this still poses a threat of infection)

407
Q

How is Ebola treated?

A

Monoclonal antibody

(New therapy!)

408
Q

Between Zika, Dengue, and Chikungunya…

Which can be vertically transmitted?

Which can be sexually tranmitted?

A

Vertical:

  • Dengue, Chikungunya, Zika

Sexual:

  • Zika