Viruses Flashcards
(85 cards)
1
Q
What are some of the human diseases caused by viruses?
A
AIDS Influenza Cervical Cancer Measles Diarrhoea Haemorrhagic fever Common Cold Hepatitis Rabies Cold sores
2
Q
What is the name given to viruses that can infect bacteria?
A
Bacteriophage
3
Q
What are the general properties of Viruses?
A
- Obligate intracellular parasite
- Replicate with host cell only
- unable to grow on synthetic media
- Host specific (cell specific - tissue tropism)
- Size 10-300 or 400nm
- Genetic material either DNA or RNA (not both)
4
Q
What are the typical structures of a virion?
A
- Spikes (projections)
- Envelope (membrane)
- Nucleic acid
- Capsomeres (capsid subunits)
- Capsid (protein coat)
5
Q
What are the two types of proteins that make up a virus?
A
- Structural Proteins
- Non-structural proteins
6
Q
What is the function Structural proteins?
A
- Make up the viral structure (Capsids which are made up of capsomeres)
- Spikes protruding through lipid envelope may have stabilizing membrane under lipid
- Facilitate entry into host cell
- Protect viral nucleic acid
- Core associated with nucleic acid
7
Q
What is the function of Non-Structural Proteins?
A
- Coded for the viral genome
- Not part of the virion, however some may be packaged in virion.
- Enzymes needed for replication.
8
Q
What are the three Viral symmetry structures a virus can be in?
A
- Icosahedral symmetry (cubic)
- Helical Symmetry
- Complex Symmetry
9
Q
What are the characteristics of Icosahedral symmetry?
A
- Solid regular sides
- 20 equal triangular sides
- Greatest number of capsomeres packed in a regular fashion
- All DNA animal viruses except poxvirus and some RNA virus.
10
Q
What are the characteristics of Helical symmetry?
A
- Spiral structure
- Capsomeres arranged in a stair case fashion
- Always contained within a lipoprotein envelope
- Glycoprotein spikes through lipid layer, connected to underlying protein by matrix (M) protein
- ssRNA viruses: influenza, parainfluenza and rabies.
11
Q
What are the characteristics of Complex symmetry?
A
- Virus with large genomes (poxvirus)
- Neither isocahedral or helical
12
Q
How do we classify viruses?
A
By the Baltimore Scheme (classes 1 to 7) based on their nucleic acids.
13
Q
What is Class 1 virus according to the Baltimore Scheme?
A
A double stranded DNA (dsDNA)
14
Q
What is Class 2 virus according to the Baltimore Scheme?
A
A Single Stranded DNA (ssDNA)
15
Q
What is Class 3 virus according to the Baltimore Scheme?
A
double stranded segmented RNA (dsRNA)
16
Q
What is Class 4 virus according to the Baltimore Scheme?
A
single stranded RNA (ssRNA) Positive sense
17
Q
What is Class 5 virus according to the Baltimore Scheme?
A
single stranded RNA (ssRNA) negative sense
18
Q
What is Class 6 virus according to the Baltimore Scheme?
A
ssRNA positive sense with dsDNA intermediate before replication (retroviruses)
19
Q
What is Class 7 virus according to the Baltimore Scheme?
A
dsDNA with positive sense, part ssDNA with ssRNA intermediate (reversviruses)
20
Q
What does “part ssDNA” mean in terms of reversviruses?
A
The SSDNA has one strand full length and the other length is shorter
21
Q
What forms can Viral Nucleic Acids come in?
A
- RNA or DNA
- SS or ds DNA
- Single molecule or segmented
- Linear or Circular
- Large or small
- packed inside or integrated unto host DNA
22
Q
What class is HIV and why?
A
HIV is a class 6 virus because the dsDNA intermediate helps this ssRNA virus to integrate itself into the host DNA before it replicates.
23
Q
In terms of Viral Nomenclature, what are the characteristics of naming a Family of Viruses and how do we write them?
A
Families share overall genome organisation, structure and replication strategy.
When writing the family of a virus:
- Family names are italicized and end in the suffix -viridae
- Some virus families have subfamily names italicized with suffix -virinae
- Some texts use English version of family names (e.g. picornoviridae become picornoviruses)
24
Q
In terms of Viral Nomenclature, what are the characteristics of naming a Genera of Viruses and how do we write them?
A
Genera of viruses chare genome organization, structure and size
When writing the genera:
- Names are italicised and end in the suffix -virus
25
In terms of Viral Nomenclature, what are the characteristics of naming the species of Viruses and how do we write them?
Species are based on nucleic acid sequence identity within a genera.
When writing the species:
- Names are not well organised and may be in numbers (e.g. Human papillomavirus 16)
26
How do Viruses replicate?
- They code for own enzymes or host enzymes to transcribe and replicate virus genome.
- They also use the hosts' synthetic machinery (ribosomes) for protein production.
27
Can viruses produce protein?
No. They can only code for it in their genome and then use the host cell ribosome for protein production.
28
How are viruses defined?
By the type of nucleic acid and their replication mode (i.e. replication of mRNA)
29
Where does virus replication take place?
Inside the host cell with host producing new viral particles.
30
what effects on the host cell does virus replication have?
Produces Cytopathic effect due to the virus hijacking the ribosomes to make protein for itself, meaning that the host cell stops making own protein having a pathological effect on the cell.
31
What is the difference between the lytic and lysogenic life cycles of viruses?
Lytic cycle (virulent) reproduce/lyse or bud out of the host cell causing lysis (cell death)
Lysogenic cycle (temperate) is when they integrate into the host cell genome (chromosome) and they stay there. Can either be prophage or provirus: Prophage is integration into host cell, provirus (HIV) is when it makes copies of itself first then it integrates into host DNA (may then come out of lysogeny and become lytic)
32
What are the stages of replication?
- Attachment - via specific receptors on host cell membrane (MUST DO THIS)
- Penetration - once inside it "uncoats" protein shell
- Replication of viral genome
- Production of late viral proteins (structural)
- Assembly of the progeny virions (maturation)
- Release of virions from cell (budding or lysis) - if host cell is enveloped then budding occurs, if it's naked then cell lysis.
33
Describe a Baltimore Class 1 virus (How it works).
Class 1 is a dsDNA
- Similar to transcription of host genome
- Usually host DNA-dependant RNA polymerase
- Early and late viral mRNA transcribed from either strand.
- Translated to early and late viral proteins respectively (early proteins from parent virus, late from replicated DNA)
34
Describe a Baltimore Class 2 virus (How it works).
Class 2 is a ssDNA:
- Host DNA polymerase produce copy of ssDNA which then binds to form dsDNA.
- Transcription follows as for dsDNA virus
- Polarity of DNA packaged is of little importance (i.e. pos and neg DNA doesn't matter because it makes a copy of itself and behaves like dsDNA).
35
Describe a Baltimore Class 7 virus (How it works).
Class 7 is a partial dsDNA and ssDNA, reversivirus:
- Made fully dsDNA by host DNA polymerase
- mRNA transcripts made by host RNA polymerase
- Virus codes for 'reverse transcriptase' which make partial DNA from RNA transcript for packaging
36
Describe a Baltimore Class 3 virus (How it works).
Class 3 is dsRNA segmented:
- Virion has packaged a virus coded, RNA-dependent RNA polymerase.
- This RNA polymerase recognizes dsDNA and transcribes negative RNA strand into positive mRNA
- More energy efficient than denaturing dsRNA
37
Describe a Baltimore Class 4 virus (How it works).
Class 4 is ssRNA positive sense:
- Genome is used as mRNA directly
- Viral proteins translated first, they they direct replication of the viral genome (opposite of other virus classes which replicate the genome first then make proteins)
38
Describe a Baltimore Class 5 virus (How it works).
Class 5 is ssRNA negative sense:
- Must produce a positive sense copy to act as mRNA
- Virion packaged virus coded, RNA-dependent RNA polymerase
- Negative sense RNA is template for positive sense RNA which acts as mRNA
- Similar to dsRNA replication
39
Describe a Baltimore Class 6 virus (How it works).
Class 6 is ssRNA positive sense, with DNA intermediate (retrovirus)
- Packaged virus coded reverse transcriptase (RNA-dependent DNA polymerase)
- dsDNA copy of RNA produced after entry into cell
- viral DNA integrated into host genome
- RNA polymerase of host used to transcribe into mRNA
40
What are the two mechanisms by which viruses cause disease?
1. Replication within the host cell leading to direct damage of the cell (leading to disease)
2. Host defences leads to cell damage as it attempts to clear the virus infected cell (immune responses)
41
What Host Cell Factors are necessary for the virus to invade and replicate?
1. Appropriate cell surface receptors:
- this determines if virus can get entry
- Viruses generally have specific tropism (specific receptors it can attach to on specific tissue types)
2. Internal cellular environment suitability:
- Molecular machinery needs to be adequate for replication
- Physical environment needs to be suitable (i.e. temp needs to be just right for the virus to replicate).
42
In terms of Viral Pathogenesis what is the Cytopathic effect?
- The effect of virus replication on the host cell. The invasion of the virus into the host cell changes the cell leading to direct damage of the cell.
- Many viruses cause CPE in host cells as as cultured cell lines
- Different viruses give rise to different types of CPE.
43
In terms of Viral Pathogenesis how does cell lyses affect the host?
- Production of virus early proteins cause shut down of host macromolecules because cell has been hijacked by virus to make proteins for the virus instead.
- Accumulation of large amounts of viral capsid proteins inhibits host cell and viral synthesis
44
In terms of Viral Pathogenesis what is Syncytia?
- Cell fusion
- Certain viruses produce specified fusion proteins which mediate entry into cell.
- These also cause plasma membrane of host cells to fuse.
- Formation of giant multinucleated cells (Syncytia)
45
In terms of Viral Pathogenesis what are the Inclusion Bodies?
- Bodies that appear in cells as a result of viral infection (some bacteria e.g. Chlamydia)
- Aggregation of mature viral particles
- Altered staining patterns at sight of virus synthesis
- Degenerative changes due to infection
- Intracytoplasmic, intranuclear or both.
46
In terms of Viral Pathogenesis what is Transformation?
- Some viruses produce cancerous or pre-cancerous like changes
- These viruses may act together with other cellular changes such as single point mutations.
- Break down of cellular regulation may be due to action of viral proteins.
47
What are cell surface Antigen Changes?
- Many viruses can induce the formation of new surface antigens on host cells as a consequence of infection.
- Mostly caused by enveloped viruses as they use these to facilitate budding out of cell.
- These may be recognized as foreign antigens and an immune response is mounted.
48
what is Immunopathology of viral infections?
It's the damage to the host which is mediated through the immune system attempting to remove the virus or viral infected cells.
49
Immunopathology of viral infections is primarily due to what?
Cytotoxic T-cells which destroy cells with virus antigenic markers (presented on surface of infected cell via Class 1 MHC)
50
What is a Cytokine storm and how does it work?
- Its the sudden outpouring of various cytokines in response to viral infection (lung infection)
- Virus replicates in epithelial cells destroying cilia leading to secondary bacterial infections.
- Immune system responds with cytokine production attracting T cells and macrophages leading to more cytokine production.
- Usually controlled by a feedback loop (IL-10) but in a cytokine storm this is uncontrolled resulting in tissue damage.
- usually caused by Influenza and SARS.
51
HIV is an infection that depresses the Immune response. Explain this process.
- Direct damage to the immune cells.
- Destroys T helper cells - CD4 cells (these are a receptor for HIV)
- Only 10% of these cells are actually infected and destroyed by HIV.
- 90% are destroyed by indirect mechanisms not clearly understood.
- This leads to destruction of adaptive immune response.
- Other infections from opportunistic pathogens or tumours cause secondary infections due to depression of immune response.
52
What are Exanthem?
Skin rashes
53
What types of Skin rashes are there?
- Vesicular eruptions - due to replication of virus and direct damage to epithelial cells (Herpes simplex virus)
- Maculopapular rash - due to destruction of virus infected cells by cytotoxic T cells (measles), these are raised red spots)
- Purpuric rashes - associated with fall of platelets due to viral infection (Rubella)
- Haemorrhagic rashes - due to disseminated intravascular coagulation resulting from viral infection (Dengue) which leads to bleeding under the skin and eyes.
54
What types of virus can cause any non-haemorrhagic skin rash?
Entro and echoviruses
55
How can viruses be transmitted?
- Inhalation
- Ingestion
- Inoculation
- Sexual contact
- Transplantation
- Vertical transmission
56
What are the 6 events of Viral Infections?
1. Invade the host
2. Replicate in cells at sight of inoculation
3. Overcome/evade local defences
4. Spread to other cells and other areas
5. Replicate again
6. Exit from host in large enough numbers to infect another host.
57
What are some factors contributing to successful invasion of viruses into host cells?
- Must cross skin or mucous membranes
- To pass into skin requires injury or trauma for entry (i.e. insect bites)
- Entry across mucous membranes easier for viruses as they often get absorbed directly into epithelial cells
58
What are some factors of the capability viruses evading the immune system?
- Poorly immunogenic due to not enough display of antigens on cell surface
- Can inactivate B cells, T cells and macrophages
- Can interfere with expression or transportation of MHC proteins
- Excess antigen production to bind all neutralizing antibodies
- Mutations that change antigenic proteins of virus (antigenic shift/drift)
- Infection of foetus before immune system develops.
59
What is a subclinical infection?
- a viral infection that is asymptomatic and is usually dealt with/cleared by the immune system with no issues.
- can exist in equilibrium within host (typhoid mary)
- can only be detected from laboratory tests such as antibody detection.
60
What are the different types of clinical disease?
- Acute non-persistent infections
- Persistent infections
- Latent infections
61
What is an Acute non-persistent infection?
An infection that is acute in onset and duration but is usually self-limiting and will resolve without intervention.
62
What is a Persistent infection?
- An infection not terminated by the immune system.
- Persistence of viral DNA in host cells
- Only DNA viruses or retroviruses
- DNA may be integrated in host DNA or episomal
63
What is a latent infection?
- an infection that lays dormant in the body.
- some latent infections never cause disease (sub clinical)
- during the latent phase they are sub-clinical
- Some infections can be reactivated causing episodes of illness.
- detection may only be possible during episode of illness
- Some latent infections lead to malignant disease.
64
What is an Insidious Infection?
An infection that effects proteins (Proteinaceous Infectious Particle - PRION).
- Caused by abnormal protein conformation
- happens via Spontaneous mutations and ingestion of infected protein (meat)
- Abnormal protein contacts with normal protein converting it to abnormal conformation (i.e. recruitment).
- Is fatal
- Long incubation periods of years to decades
- Effects the CNS causing Spongiform Encephalopathies
65
What are the types of incubation periods and why are they important?
Types:
- Short: less than a week, usually localized infections
- Medium: 7-21 days, generalized infections
- Long: weeks to months
Important as an aid to diagnosis and tracing spread.
66
How is the infectiousness of a virus now described?
By the Reproduction number or R0
67
What is the R0?
The average number of secondary cases generated by one primary case in a susceptible community.
68
What Baltimore class are Herpes Viruses?
Class 1 ds linear DNA
69
How do Herpes Simplex Virus (HSV) gain entry into the host cell?
- Attachment by envelope glycoproteins (gB, gC, gD attach and trigger fusion of viral envelope to cell membrane: gB, gH and gL)
- Nucleocapsid enters cytoplasm (with some tegument)
- Transported to nucleus where the viral DNA is released and enters the nucleus via nuclear pores and circularizes.
- Empty capsid lasts for several hours in cytoplasm and is eventually broken down.
70
How does Herpes Simplex Virus (HSV) gene expression work?
- The protein VP16 (in tegument) activates the alpha phase, however need host proteins Oct1 and HCF
- The genes are expressed in phases:
- alpha genes, immediate early, are regulators of gene expression. These turn on Beta genes.
- Beta genes early stage proteins for DNA replication. These turn on gamma genes.
- Gamma genes, late structural proteins, contain VP16 which re-initiates the cycle.
- Each phase that is activated by the previous one also inhibits the previous phase.
- Assembly in Nucleus and released through Endoplasmic Reticulum.
71
How does Herpes Simplex Virus (HSV) latency work?
- Activation of HSV genes in neurons is limited (failure to express alpha genes)
1. Latency Associated Transcripts (LAT's): Short RNA fragments from virus (produced from spliced longer RNA's) that interfere with alpha genes.
2. VP16 fails because HCF is cytomplasmic in sensory neurons.
72
How does Herpes Simplex Virus (HSV) reactivation work?
•Exact mechanism is not understood
•Induced by local or systemic stimulation
–Physical / emotional stress, UV light, hyperthermia etc
•Low levels of viral transcripts in neurons
•Virus transported down axon to end mucosal site
•Virus buds out of neuron and into surrounding cells where it is able to go into lytic cycle
73
What Baltimore class of virus is Influenza?
•Class 5, ss(-) RNA segmented genome (8 segments), replicates in nucleus.
74
What family and genus does Influenza virus belong to?
•Family: Orthomyxoviridae,
| Genus: Influenzavirus
75
What symmetry/structure can Influenza be?
•Enveloped, helical capsid, spherical or filamentous (pleomorphic)
76
What is the Nomenclature of Influenza based on?
Based on type, location of first isolation, isolate number, year, and H,N.
e.g A / Singapore / 6 / 86 (H1N1).
77
What are the serological types of Influenza?
Three serological types based on nucleoprotein (NP) and matrix protein (MP): A, B and C. Further typed based on H and N.
78
What are the two surface peptides (proteins) Influenza?
–Haemagglutinin H (15) and neuraminidase N (9)
79
Where in the body and what type of tissue does Influenza infect?
infects the columnar epithelium of RT
80
What is the incubation period of influenza and what are the associated symptoms?
incubation period 1-4 days, then sudden onset of fever, headache, chills, muscle aches, sore throat, cough (mild to very severe). Usually no coryza (runny nose) which is associated with common colds.
81
What is the Infection Process of Influenza?
•Binding to cell
–Haemagglutinin on surface of virion
–Binds sialic acid residues on mucus membranes (also on RBC –agglutination)
–Haemagglutinin also causes fusion and entry within endosomal vesicle
•Release of viral genome
–M2 protein forms a channel in virus envelope allowing H+ions to enter (reduce pH)
–Low pH weakens M1 (matrix protein) bond to release nucleocapsid (each segment of RNA has nucleocapsid)
•Each segment of RNA is bound to a nuleocapsid protein (NP) which transports it to nucleus for replication
82
How does Influenza Replicate?
•Occurs in nucleus
•After transporting to nucleus
–Negative RNA is template for positive RNA which is mRNA
•mRNA sent to cytoplasm for translation
•Progeny nucleocapsid sent to cytoplasm where assembly occurs at the plasma membrane
•Neuraminidase (NA) involved in release of virions
83
Name the three types of Influenza virus and their Primary hosts.
* Type A: primarily avian crossed into mammals (birds have greatest range of types). H undergoes minor (annually) and occasionally major changes, some variation in N. Epidemics 1-2 yrs, occasionally pandemic (birds, pigs, humans).
* Type B: human is only host, epidemic 3-5yrs.
* Type C: human, rare, mild illness.
84
In regards to Influenza Genetic Variations what is the difference between Antigenic Drift and Antigenic SHift?
* Antigenic Drift: minor changes due to host immune selection of mutants with slightly altered H & N (every 2-3 yrs). Types A and B.
* Antigenic Shift: major change in H & N due to recombination between human and animal types. Segmented genome increases chances of reassortment (interchange of gene segments of two viruses in one cell). Humans/birds/pigs. Type A.
85
How is Influenza diagnosed and Treated?
•Diagnosis:
–Early treatment, prevent spread, epidemiology
–Clinical / Surveillance
–NPA, Respiratory washings, Swabs
–Culture on MDCK cells on cover-slip and IF
–PCR (RT-PCR), commercial kits, DNA sequencing.
•Treatment:
–Palliative –rest, liquids, avoid alcohol and aspirin (liver disease with flu)
–Antivirals –oseltamivir, anamivir, rimantidine
•Amantadine both prophylactic and therapeutic (blocks M2 ion channel)
–Vaccine –changes yearly (due to antigenic drift), does not cover all strains and takes 6 mth to produce.
