Virology Flashcards

1
Q

Viral envelope: influenza virus

A
  • Hemagglutinin: surface glycoprotein, attaches to sialic acid residues of host cell surface
  • Neuraminidase: surface spike, aids in release of virus from host cells
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2
Q

Viral proteins: matrix proteins

A
  • links envelope and capsid: stabilisation
  • can drive final assembly process
  • important determinant of budding location
  • viral capsid is made of proteins, which assemble without E requirement
  • Capsids can be icosahedral or helical
  • Icosaheral viruses have 20 facets (each an equilateral triangle. and 12 vertices, which results in 5- 3- and 2-fold symmetry.
  • All known human viruses w helical capsids are naked.
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3
Q

DNA viruses

A
  • Enveloped (dsDNA)
    • Pox
    • Herpes
    • Hepadna
  • Naked capsid (dsDNA)
    • polyoma
    • papilloma
    • adeno
    • parvo
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4
Q

RNA viruses

A
    • RNA
      • Naked
        • Picorna
        • Calici
      • Enveloped
        • Toga
        • Flavi
        • Corona
    • RNA
      • Enveloped
        • Rhabdo
        • Filo
        • Orthomyxo
        • Paramyxo
        • Bunya
        • Arena
  • +/- RNA
    • double capsid
    • reo
    • RNA via DNA
      • Retro (enveloped)
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5
Q

Baltimore classification of viruses: Class I

A
  • Class I: dsDNA
    • Papilloma, polyoma, herpes, adeno, pox
    • some can transform cells
    • host enzymes transcrobe IE or E mRNA
    • E-proteins: replicate parental DNA & late (L) mRNA;
    • L-proteins: assemble into capsids
    • Capsids: incorporate the viral DNA to make mature virus
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6
Q

Class II

A

Class II: ssDNA

  • very small (parvum=small), circo- or parvo-virus (linear so susceptible to DNAses)
  • replication occurs in nucleus
  • form a (-) strand -> template for (+) strand
  • require cell enzymes
  • mRNA translated into viral proteins
  • NOTE: no immediate early or early proteins
  • viral proteins: make up capsids
  • viral DNA is encapsidated in progeny virus
  • Parvovirus can only replicate when cells are actively replicating
  • icosahedral, non-enveloped
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7
Q

Class III

A

Class III: ds RNA Virus

  • dsRNA: cannot function as mRNA; class III must package an RNAP to make mRNA after infection of host cell
  • genomes segmented
  • RNA-dependent RNAP in virion
  • Ex. Reo-, Birnaviruses, rotavirus
  • ds RNA -> transcribed to viral mRNA (v-mRNA) by virus-associated RNA-dependent RNAP
  • v-mRNA: translated to structural and non-structural proteins:
    • viral proteins to form immature capsid
    • mRNA packaged into immature capsid, then copied w/in capsid to form ds RNA
  • Rotaviruses, members of Reoviridae
    • acute gastro in infants and young children
    • icosahedral
    • 11 dsRNA segments
    • RNA replication: concurrent w packaging of genome segments
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8
Q

Class IV

A

Class IV: (+) sense RNA viruses

  • Divided into IVa & IVb
  • always infectious w/o viral proteins
  • ends of genomes often modified w caps
  • Ex. Picorna-, toga-, corona-, flaviviruses, dengue

IVa

  • polyprotein: post-translational cleavage make multiple viral proteins
  • non-structural proteins: transcribe parental (+) RNA into (-) RNA whih in turn is transcribed to (+) RNA
  • Structural proteins: make up capsids, incorporate viral RNA - progeny virus

IVb

  • stuctural proteins (not one polypeptide)
    • parental RNA transcribed into (-) RNA by viral non-structural proteins
    • ss (-) RNA -> transcribed into (+) RNA (many copies)
  • Capsid incorporates the (+) RNA, other viral proteins -> progency virus

IV: Picornaviruses

  • naked, small, icosahedral
  • genome is mRNA (naked genome is suffcient for infection)
  • virus replicates in cytoplasm, most are cytolytic
  • v-RNA: translated into polyprotein; cleaved into enzymatic & structural proteins
  • include poliovirus, hepA, rhino- and enteroviruses
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9
Q

Class V

A

Class V: ss (-) sense RNA viruses

  • more diverse than + sense, larger
  • segmentation common
  • genome by virus-specfic polymerase (premade); reads (-) RNA -> forms (+) RNA
  • assembly of capsid -> incorporation of genomic RNA and viral proteins, including the virus RNAP -> progeny virus
  • Ex. Filiviruses, Orthomyxo-, Bunya- (Hantavirus), Paramyxo-viruses
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10
Q

Class VI

A

Class VI: ss (+) sense RNA viruses (RT)

  • 2 copies of +ve strand RNA (not ds); premade RT generates ds provirus
  • retroviruses (HIV)
  • Provirus: integrates into host genome, template for synthesis of viral mRNA
  • Viral mRNA: viral non-structural and viral structural proteins
  • not directly infectious on its own
  • Non-structural proteins: may be RT and other polymerases
  • Structural proteins: assemble into the capsid
  • Mature virion: the capsid incorporates viral genome AND the nucleoproteins including RT -> progeny virus
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11
Q

Class VII

A

Class VII: ds DNA viruses, ssRNA intermediate, RT

  • Ex. Hepadnaviruses (HBV)
  • VII: partially ds DNA virus comes in w its own RT
  • core is stripped of nucleic acids
  • fills in gaps
  • ds supercoiled DNA
  • pre-genomic RNA
  • structural proteins made and then assemble into a capsid
  • pre-genomic RNA goes into capsid; this is ss
  • maturation: RT makes a RNA-DNA hybrid in capsid
  • RNAase activity digests RNA
  • DNA polymerase activity makes the partially dsDNA
  • comes out of Golgi and goes out of cell
  • VII: HBV
    • enveloped virion w partially ds circular DNA genome
    • replication is thru a circular RNA intermediate
    • virus encodes and carries RT
    • HBV has a strict tissue tropism to liver
    • HBV genome can integrate into host chromosome
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12
Q

Defective virus

A
  • complete virus particle BUT unable to replicate w/o helper virus (lacks full complement of genes for complete lifecycle)
  • Ex. Hep D requires Hep B to replicate
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13
Q

Pseudovirions

A
  • contain non-viral DNA, infectious but do not replicate
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14
Q

Viroids

A
  • infectious, subviral particles
  • small, circular ssRNA genomes
  • mainly cause plant diseases
  • Hep D appears to be a viroid-lke entity (enclosed in Heb B)
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15
Q

Virophage

A
  • Sputnik: 18 kb circular ds DNA, icosahedral virus (50 nm)
  • grows only in a strain of mimivirus w/in infected amoeba
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16
Q

Host defenses

A
  • non-specific
    • interferon
      • Type I: IFN-alpha & beta
      • Type II: IFN-gamma aka macrophage activation factor
    • complement
    • other cytokines
  • specific
    • Ab production
    • specific immune system
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17
Q

Immunopathology

A
  • immune response to viral infection can cause tissue injury, i.e. group specific Ab from previous infection actually protect virus.
    • Ex. CMV (circulating immune complexes -> depositis -> arthritis)
    • Ex2. Dengue (hemorrhagi shock sydnrome: fixation of complement by circulating immune complexes -> release of products via complement cascade -> sudden increase in vascular perm, shock, death
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18
Q

Persistent infection & latency

A
  • Persistent infection: Ex. Adenovirus; not totally resolved so certain number of viruses constantly produced; infection w/o cell death, selection of ideal target cell subsets (chronic - nonlytic, productive); viruses apply numerous avoidance strategies to persist
    • direct selective pressure to suppress infected host’s innate and/or adoptive immune system
    • viruses can alter/interfere w the processing of viral peptides by professional APC
    • can downregulate co-stimulator and/or MHC molecules (required or T cell signaling)
    • inhibit the differentiation of dendritic cells; infect effector T and B cells directly.
  • Latency: virus goes there and hides even when host is healthy; recurrent infection;
    • modulation of viral gene expression
    • viral subversion of cell apoptotic pathways
    • avoidance of clearance by immune system
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19
Q

Basic steps of viral disease

A
  • acquisition
  • initiation of infection at primary site
  • incubation period (amplification, spread to secondary site)
  • replication in target tissues
  • immune response (limit & contribute)
  • transmission
  • resolution or persistent infection
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20
Q

Site in Viral Disease: GIT

A

GIT: Ex. Rotavirus (class III)

  • no sx -> gastroenteritis, vomiting, diarrhea
  • transmission: fecal, especially in daycare, resp. possible
  • At risk:
    • Infants < 24 mo
    • Older children & adults: at risk for mild diarrhea
    • Undernourrished
  • Rotavirus resistant to environmental and GI conditions
  • asymptomatic infection -> virus release
    *
21
Q

Sites in viral disease: Exanthems & hemorrhagic fevers

A
  • virus-induced skin disease
  • major classifications of viral rashes
    • macules: spots
    • papules: raised
    • nodules: larger raised
    • vesicular lesions: blisters containing virus
  • hemorrhagic fevers -> infect endothelial cell lining of the vasculature, possibly compromising the structure of bv
22
Q

Organ example: HBV

A
  • enveloped virion w partially ds, circular DNA genome
  • replication is through a circular RNA intermediate
  • virus encodes and carries RT
  • HBV has a strict tissue tropism to the liver
  • HBV genome integration into host chromosome
23
Q

Sites in viral disease: CNS

A

Ear infections and blood infections spread to brain
Ex. encephalitis, viral meningitis,
Ex. Herpes producing cerebral hemorrhage

24
Q

HHV-1 & HHV-2: CNS & STI example

A
  • Both HHV-1 &-2 (HSV-1 & 2) large ds DNA enveloped icosahedral virus
  • can initially infect and replicate in mucoepithelial cells
    • lytic (most cells: Cowdry type A inclusion bodies, syncytia)
    • persistent (lymphocytes & macrophages)
    • latent infections (neurons)
  • virus blocks effects of interferon, prevents CD8 T-cell recognition of infected cells, escapes Ab neutralisation and clearance by going into hiding during latent infection
  • Latency in CN V and then triggered.
25
Q

HHV-5 (CMV): eye

A
  • Pink eye due to adenovirus (HHV-5) infection
  • chorioretinitis associated w CMV in newborns
  • most prevalent viral cause of congenital disease
  • Affected newborns show:
    • small size, thrombocytopenia, microcephaly, intracerebral calcification, jaundice, hepatosplenomegaly (HSM), and rash
26
Q

Examples of viruses transmitted in blood

A
  • Hep B, C, G, D
  • HIV
  • HTVL-1
  • HHV-5 (CMV)
  • HHV-4 (EBV)
  • W. Nile encephalitis virus
27
Q

Host cell changes in response to viral infection: Cytopathic effects (CPE)

A
  • rounding
  • inclusion bodies
    • Ebola virus inection: liver inclusion bodies
    • GI hemorrhage due to CMV: stomah
  • cell lysis, necrosis, apoptosis
  • syncytia formation
  • transformation
  • Giant cells
    *
28
Q

Cancers due to viral infections

A
  • HPV -> cancers of cervix & oral cavity
  • HBV & HCV -> HCC
  • EBV -> Gastric cancer, nasopharyngeal carcinoma, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma
29
Q

Tumour viruses: Transformation

A
  • loss of growth control
  • reduced adhesion
  • motility
  • invasion
  • ability to form tumours
  • Transformed cells frequently exhibit chromosomal aberrations
  • Lytic stage -> Late proteins
    Transformed -> early proteins -> stopped -> then undetectable
30
Q

Early function proteins are involved in transformation

A
  • Papilloma: oncoproteins E6 & E7
    • E6 modifies p53 & hTERT
    • E7 modifies pRB
  • Polyoma: large T and small T antigen
    • polyoma virus have ds circular DNA
  • both early and late proteins expressed during lytic
  • only late proteins expressed in transformation
  • Adenovirus: E1A and E1B
  • BK virus: Large T
  • SV-40: Large T
31
Q

EBV (HHV-4)

A
  • >90% of EBV-infected people intermittentl shed the virus for life (even asymptomatic)
  • approx. 70% of the US population infected by age 30
  • causally associated w endemic Burkitt’s lymphoma (AfBL), Hodgkin disease, nasopharygneal carcinoma (NPC)
  • has 3 potential outcomes:
    • replicate in B cells or epithelial cells permissive or EBV replication
    • cause latent infection of B cells in presence of competent T cellls -> Downey cell association (atypical T cells, enlarged cell & nucleus)
    • stimulate and immortalize B cells
    • Note: both B- & T-cells required for antigenpresentation
32
Q

HHV-8 (KSHV): Kaposi’s sarcoma

A
  • tumour of bv wall
  • rare in people not infected w HIV
  • common in HIV+ people frequently detected tumour in AIDS Pt
  • pink, red, or purple lesions on skin and mouth
33
Q

Merkel cell polyomavirus (MCV)

A
  • Merkel cell carcinoma (MCC) highly aggressive neuroendocrine carcinoma of skin w a high propensit of recurrence and metastasis
  • 5-year disease-specific survival rate ~60%
  • MCV associated w most MCC cases (subset of MCC, 20 - 30%, do not harbour MCV and apparently have a distinct pathoetiology)
34
Q

Hep B (DNA)

A
  • each of the hepatitis viruses infects and damages the liver
    • classic sx of jaundice and release of liver enzymes
  • spread by blood or needles, sex, and perinatally; also in tears, semen, vaginal.
  • median incubation period of ~ 3 mo, after which icteric sx start
  • chronic hep follows in 55 to 10%
  • 1/3 of world’s pop has been infected w HBV -> 1 to 2 million deaths/r
  • incidence of HBV is decreased (development, use HBV vaccine)
  • strict tissue tropism to liver
    • HBV produces HBx protein to regulate apoptosis, proliferation, genetic instability to stay in host liver and produce small amounts of virus continuously
  • can integrate into host chromosome
35
Q

HCV

A
  • HCV transmission -> develop cancer 10 to 50 years (median 30 years)
  • flavivirus (class IV) w (+) ss RNA genome
  • Exception: only flavivirus not transmitted thru insects
  • continual liver repair, induction of cell growth during chronic HCV infection
36
Q

RNA tumour viruses

A
  • some retroviruses have oncogenes in addition to regular genes
  • retroviruses - particularly oncovirinae
  • Ex. HTLV-1 -> leukemia
    • cause cancer after >30 y latency
    • promote cell growth in more indirect ways than oncogene-encoding viruses
    • associated w non-neoplastic neurologic disorders and other disease
    • adult acute T-cell lymphocytic leukemia (ATLL) & HTLV-1 associated myelopathy (tropical spastic paraparesesis)
    • Tax: transcriptional regulator -> activates promoters including IL-2 & IL-2R
    • integrates near cell growth-controlling genes
37
Q

Non-Hodgkin’s lymphoma

A
  • viral infections: HTLV-1, Hep C, and EBV, increase the risk of developing non-Hodgkin’s lymphoma
38
Q

Hep C (RNA)

A
  • produces the following proteins:
    • core to regulate apoptosis
    • NS2 -> proliferation
    • N55B -> genetic instability
  • HCV transmission -> develop cancer: 10 to 50 years (median 30 years)
  • HCV is a flavivirus (class IV) w a (+) ss RNA genome
  • Exception: only flavivirus not transmitted thru insects
  • acute HCV infection can go 3 routes:
    • Recovery & clearance (15%)
    • Cirrhosis rapid onset (15%)
    • Persistent infection (70%) of which 40% asymptomatic leading to chronic hepatitis, further leading to
      • liver failure
      • cirrhosis
      • Primary hepatocellular carcinoma (PHC)
39
Q

Viral vaccines: attenuated

A
  • altered (mutated) to non-pathogenic form
  • tropism altered -> no longer grows at a site to cause disease
  • Polio (Sabin), MMR, Yellow fever, Rotavirus, Varicella
40
Q

Viral vaccines: inactivated

A
  • rendered non-pathogenic usually by chemical treatment such as w formalin that cross-links viral proteins.
  • Ex. Hep A, Influenza, Polio (Salk)
    • influenza vaccine: trivalent inactivated vaccine (TIV), however live attenuated vaccine is more effective
41
Q

Viral vaccines: subunit

A
  • Virus Like Particles (VLPs)
  • HepB
  • Quadrivalent HPV 6/11/16/18 L1 VLP (Gardasil)
  • HPV vaccine
    • Recombinant L1 proteins that self-assemble into VLPs
    • Admin. before onset of sexual activity, then 2x after (~100%) protection from infection w vaccine HPV types.
    • Potential to prevent ~70% of cervical cancers, ~90% of genital warts.
42
Q

Viral vaccines: DNA

A

2 ways:

  • take viral DNA, circularize into plasmid, plasmid coated w gold particles and injected
  • take viral gene and splice into another vector. ex. vaccinia virus
43
Q

Viruses treatable w antivirals

A

Herpessimplexvirus
• Varicella-zostervirus
• CMV
• HIV

  • Influenza A and B viruses
  • RSV
  • HBV & HCV
  • Papillomavirus
  • Picornavirus
44
Q

Targets for antiviral drugs

A
  1. Recognition & attachment: Ab-receptor antagonists
  2. Uncoating: Amantadine, Arildone, Rimantadine, Tromantadine
  3. Transcription: interferon, antisense, oligomers
  4. Replication: nuceloside analogues (guanosine), AZT, Acyclovir
  5. Protein synthesis: interferon
  6. Fusion: Tromantadine, Enfuvirtide
  7. Assembly: protease inhibitors
45
Q

Antivirals: blocking viral replication

A

nucleoside analogues: incorporated into viral genomes -> inhibition of function of viral DNAP.

  • chain termination: analouges lack hydroxyl groups for linking of backbone,
  • Ex. Acyclovir for HHV-I & HHV-II: Guanosine analogue, must undergo TK-mediated phosphorylation (Acyclovir triphospate)
  • Nucleoside inhibitors of RT
  • Ex. AZT
  • Ex2. ddl
  • Non-nucleoside polymerase inhibitors
  • Ex. Nevirapine binds to various sites on enzyme
46
Q

Antivirals: blocking assembly and release

A
  • Ex. protease inhibitors (Saquinavir)
    • block cleavage of polyproteins
    • HIV is dependent on proteolytic enzyme for full infectivity
    • Drug-resistant strains > protease mutations
47
Q

Control of viral diseases: immunomodulators

A
  • Interferons:
    • IFN-alpha: active against many viral infections (Hep A, B, and C, HSV, HPV, and rhinovirs)
  • Imiquimod
    • TLR ligand, stimulates innate responses to attack the virus infection (HPV)
48
Q

Rationale behind antiviral cocktails

A

CART & Highly Active Antiviral Treatment (HAART)
- multiple mechanisms to control viral diseases