Viruses Flashcards

1
Q

What are the seven viral groups by Baltimore classification and give an example of each?

A

1) dsDNA e.g. herpesvirus family
2) ssDNA e.g. parvovirus
3) dsRNA e.g. rotaviruses
4) + sense RNA e.g. HCV, polio
5) - sense RNA e.g. influenza, ebola
6) RNA RT e.g. HIV
7) DNA RT e.g. HBV

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2
Q

What are the 4 courses of viral infection?

A

Acute - influenza One bump at start. 99% of viral infections are acute, acute and resolving.
Persistent infection, smoldering
Persistent infection, latent e.g. Herpes simplex virus, cold sores
Persistent infection, slow e.g. Measles, HIV

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3
Q

What is the prodromal response to infection?

A

Most common symptoms of viral infection are due to general effects of innate immune responses. Fever, fatigue, sleep, mobilisation of lymphocytes, acute phase proteins.

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4
Q

What is antigenic drift?

A

Antigenic drift is the gradual accumulation of mutations.

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5
Q

What is antigenic shift?

A

Sudden change in antigenic type. When two or more strains of a virus combine to make a totally new type, by using the antigens of the original strains combined.

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6
Q

What types can capsids be?

A

Simple and complex, helical or icosahedral.

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7
Q

Where does the virus life cycle occur?

A

Entirely within the host cell.

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8
Q

What can virus characters be described as in terms of time?

A

Chronic, latent or lytic.

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9
Q

At what stage in its lifecycle is a virus infectious?

A

As a virion

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10
Q

What are the stages to the virus life cycle?

A

Entry, Replication, Assembly and Release.

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11
Q

How do retroviruses infected human cells?

A

make DNA reverse transcript of their RNA genome before doing anything else. This is then integrated into the chromosomal DNA. Infection is therefore irreversible.

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12
Q

What is the difference between naked and enveloped viruses?

A

Viruses that replicate by bursting cells – lytic infection – tend to be naked particles i.e. capsid with spikes. Viruses that bud chronically from sick cells tend to pick up a membrane as they leave and so are called enveloped.

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13
Q

How does influenza rearrange its genes?

A

Antigenic drift is the gradual accumulation of mutations which happens in flu due to selective pressure. Over a series of flu seasons the virus gradually changes into a strain able to evade abs originally there, at which point it may reinfect.
Type A flu can use drift and shift which causes most pandemics.

Because of its segmented genome, human influenza also infects birds and pigs. So human, bird or pig flu co-infected the same organism resulting in re-assortment of the individual segments is possible. This is antigenic shift and can lead to a new strain of flu. Happens every 10-30 years.

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14
Q

What are viruses?

A

Obligate intracellular parasites

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15
Q

What are the immune mechanisms used by the immune system to fight off viruses?

A

Innate: IFNα, β limit the infections
NK cells identify stress signals and recognise virally infected cells.
Adaptive: CD8 and CD4 recognise and destroy virally infected cells, resolve acute infection, carry out immunosurveillance for latent viral infections. CD4 important for humoral immune responses and Abs for re-infection with viruses.

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16
Q

What are the 3 main parts to a virus?

A

Nucleic acid surrounded by protein shell - capsid and sometimes in turn surrounded by a membranous envelope.

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17
Q

What are RNA sense and antisense?

A

RNA sense is same as mRNA so can be immediately translated in the host cell. Anti-sense RNA must first be converted to sense RNA, by RNA polymerase before translation. Some viruses have a bit of both called ambisense.

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18
Q

What are the 3 viral components synthesised in the host cell once it has entered?

A

Eclipse phase:

1) essential replication factors needed for genome synthesis
2) subunits that are assembled to form new capsids and virions - structural proteins
3) copies of the viral genome, which are packaged into new capsids.

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19
Q

What does flu bind to?

A

2-6 Sialic acid receptor for human flu

20
Q

What are virally encoded disruption of the host cell (VEHCS)?

A

By definition viruses disrupt all of host cell normal metabolism -just how much defines how pathogenic a virus is to that cell. Nearly all non-enveloped viruses - totally destroy target cell by lysis. Lytic infection is associated with extremely high amounts of virus production e.g. polio.

21
Q

What is the difference between chronic and latent virus?

A

Chronic is producing virions

Latent virus does not replicate but remains quiescent in the infected cell often for decades.

22
Q

How are viruses detected in the lab?

A

PCR

23
Q

What does the Red Queen Hypothesis say?

A

The parasite is in a constant arms race with its host (the human immune system) in order to maintain itself. This interplay of host and parasite can persist in a “meta-stable” state for years (for HIV, until the host immune system fails).

24
Q

What group is HIV in, is it enveloped and how many types are there?

A

HIV is in group 6, enveloped RNA retrovirus, whose single stranded sense RNA CAN’T serve as mRNA when entering. There are 2 types HIV-1 - most virulent and HIV-2.

25
Q

What shape does the capsid of HIV have?

A

Icosahedron

26
Q

What receptors does HIV bind to?

A

CCR5 and CD4. It infects cells which express these molecules, macrophages and CD4 T cells.

27
Q

How does HIV cause disease?

A

HIV infection of macrophages and CD4 cells leads to gradual destruction of all cells which express these markers, leading to immune dysfunction and a complex pattern of disease collectively called AIDS.

28
Q

What cell surface proteins does HIV have and what receptors do they bind to?

A

gp120 which binds to CD4 first, then to co-receptor CCR5 and gp41

29
Q

Why is HIV infection irreversible?

A

The RNA genome forms a template for RT into DNA. These are the only RNA viruses whose genome does not serve as mRNA template on entering host cell. Once integrated into host cell genome, DNA provirus is transcribed exactly as other cellular genes. Retroviruses have evolved a number of transcriptional and post transcriptional mechanisms to allow control of expression of their genetic info.

30
Q

What is the lifecycle of HIV?

A

CD4 and CCR5 tropism.
Glycoproteins gp120 is surface and gp41 is TM.
GP120 - CD4 binding leads to conformational change in GP120 exposing part of gp41 allowing GP41 to bring virus close to cell and bind to cell and allow fusion of envelope with membrane.
Release of capsid into cytoplasm, RNA–>DNA, integration, making of RNA from integrated viral DNA and translation in ribosomes to make viral proteins as well as making structural viral proteins in RER. Both come together to form a new virion that will bud off. Protease will be packed into emerging virions to cleave the gag protein into smaller ones - this is essential for the virions to be infectious.

31
Q

Does HIV go into latency?

A

NOoooooooooOoOo

32
Q

How many genes does HIV have?

A

9, 3 major ones are

1) capsid one
2) polymerase, integrase and protease
3) envelope for structural proteins

33
Q

How do antiviral nucleoside analogues work?

A

Inhibit reverse transcription and delay and disrupt the process.

34
Q

How do protease inhibitors work?

A

By stopping protease action which acts after new virion release to cut up the gag protein into mutliple small proteins that make it infectious.

35
Q

Why is it so hard to eradicate HIV?

A

In addition to genome integration, its extreme speed of antigenic drift. In the 1-2 weeks it takes the immune system to respond to virus antigens, virus population has accumulated enough antigenic change to escape from the abs and CTLs. This arms race can be slowed by HAART.

36
Q

What are the clinical HIV phases?

A

acute seroconversion - infection is established and initial proviral reservoir created. Patients often have fever, flu-like symptoms, rash, diarrhoea, high levels of virus in the blood and transient loss of CD4. Abs and CD8s reduce this viraemia to a set point where viral load is relatively stable. The amount of virus is prognostic indicator of future progression.
asymptomatic infection - 7-15 years, no ill health but slow decline of CD4 count, patients become increasingly immunodeficient
AIDS - critical point of CD4 numbers, immune system beings to fail, patient develops spectrum of infections, if not treated–>fatal.

37
Q

What is the main aim of HAART with respect to the Red Queen Hypothesis?

A

Slow down the arms race between the virus and the immune system

38
Q

What is HAART?

A

Multi drug combination, where 3 or more drugs with distinct resistance profiles and differing target genes are co-administered. Typically: 2 NRTIs + 1 NNTRI or 2 different NRTIs and 1 PI. Transforms symptoms of AIDS to partially reversible and associated immunodeficiency can be delayed in most cases.

39
Q

What is the aim of HIV therapy?

A

To repress viral load and extend lifespans. Cessation of therapy in these patients usually leads to rapid viral rebound.

40
Q

What is HIV: latent, chronic or acute?

A

Chronic

41
Q

Is herpes, chronic, latent or acute?

A

Latent

42
Q

What group is herpesviruses in, shape of capsid, how many pathogenic groups?

A

It’s a dsDNA virus so group 1, icosahedron.

8 pathogenic groups: HSV-1, HSV2, VZV, cytomegalovirus, EBV and 6, 7, KSHV.

43
Q

What are the predominant immune responses to these viruses?

A

CD8 and CD4 T cells?

44
Q

What herpesvirus group do we have vaccines for?

A

Vazircella Zoster virus - cause of chicken pox in children and of shingles on re-activation in adults.

45
Q

HSV1, 2 and 3 (VZV) - tell me bit about them.

A

HSV1 and 2 cause cold sores or genital sores in infected individuals
HSV-3 or VZV causes itchy rash pots which turn into fluid filled blisters.

All 3 of them infect neurons and reactivate periodically in response to stress factors. In VZV reactivation presents as shingles rather than chicken pox and occurs when cell mediated immune response is weakened e.g. old age.

46
Q

Which is HSV-4? Tell me a bit about it?

A

EBV infects B cells –> can transform the giving lymphoma. normally T cells kill them and very few people get lymphomas.