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POM IMMUNOLOGY > Anti-Virals > Flashcards

Anti-Virals Flashcards

1
Q

What are viruses?

A

Infectious obligate intracellular parasites
- 10,000 nucleotides, 10 genes

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2
Q

What type of genome do viruses have?

A

A virus has a genome that comprises DNA or RNA.

Within an appropriate cell, the viral genome is replicated and directs the synthesis, by cellular systems, of more viral components and genomes.

The components affect the transport of replicated viral genomes through the environment to new host cells.

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3
Q

How many nucleotides and genes do humans have?

A

3 billion nucleotides, 100,000 genes

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4
Q

How do you prove a virus causes a disease?

A

The microorganism must be found in large numbers in all diseased animals, but not in healthy ones.
The organism must be isolated from a diseased animal and grown outside the body in a pure culture.
When the isolated microorganism is injected into other healthy animals, it must produce the same disease.
The suspected microorganism must be recovered from the experimental hosts, isolated, compared to the first microorganism, and found to be identical.

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5
Q

What are different virus morphologies?

A

All viruses have a protein capsid to protect its nucleic acid
Enveloped/ non-enveloped

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6
Q

How are viruses named?

A

the disease
the person who discovered it
the place it was discovered
the part of the body affected
the way it was spread

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7
Q

How does DNA become protein, roughly?

A

DNA-> RNA = transcriptase
RNA-> protein= ribosomes

genome–> negative sense RNA–> mRNA–> protein

note some viruses never have DNA

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8
Q

What are the consequences of viral genome type?

A
  • RNA viruses and retroviruses use their own polymerase to replicate. These lack proof-reading capacity leading to high mutation rate.
  • RNA viral genomes are limited in size due to inherent instability to RNA vs DNA. The largest RNA viruses are coronaviruses genome size around 30kb. RNA viruses often use complex coding strategies to make more proteins than expected from a small RNA genome.
  • DNA viruses have genomes up to 100s kb. There is plenty of room for accessory genes that can modify the host immune response. These genes are often lost in passage in culture.
  • Segmented genomes allow an additional easy form of recombination known as reassortment, but also impose more difficult packaging strategies. Influenza has 8 different RNA segments, rotavirus has 11.
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9
Q

What is a generic virus replication cycle diagram?

A
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10
Q

What is the replication cycle of HIV-1?

A
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11
Q

How does the influenza virus fuse with a cell?

A

via endocytosis

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12
Q

What is the influenza virus replication cycle?

A
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13
Q

What is the cytopathic effect?

A

refers to structural changes in host cells that are caused by viral invasion

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14
Q

What causes the cytopathic effect?

A

usually a result of the virus lysing the cell
- this could be due to shut down of host protein synthesis or accumulation of viral proteins

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15
Q

When investigating viruses what do they form?

A

plaques in cell monolayers

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16
Q

how can you investigate viruses?

A

the plaque assay

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17
Q

What viruses often fuse cells together?

A

Viruses with surface proteins that can fuse at neutral pH often fuse cells together

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18
Q

How do you detect viral genome?

A

PCR

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19
Q

How do you detect viral antigen?

A

IFA, ELISA

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20
Q

How do you detect virus particles?

A

EM, HA

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21
Q

How do you detect virus cytopathic effect in cultured cells?

A

virus isolation

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22
Q

How do you detect antibodies to virus?

A

serology

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23
Q

Which anti-viral has the highest level of specificity?

A

Acyclovir

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24
Q

What condition is acyclovir used to treat?

A

Herpes

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25
Q

Why is acyclovir so specific?

A

Given to patients in the unphosphorylated form, has to be phosphorylated from ACV to ACVMP, this is only done by thymidine kinase which is an enzyme only found in virally infected cells

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26
Q

How does acyclovir work as antiviral?

A

Works as a nucleoside analogue - acts as a chain terminator as it lacks an OH group in the 3’ direction meaning phosphodiester binds cannot form, preventing viral replication

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27
Q

What is a nucleoside inhibitor?

A

Molecule which looks like a nucleoside and is therefore incorporated into the genome, but actually inhibits viral replication

28
Q

What is RNA in the negative sense?

A

A strand of RNA which is complementary to the mRNA

29
Q

What sense of genetic material can ribosomes translate?

A

Positive sense

30
Q

What is a virion

A

A virus particle outside the cell

31
Q

Why can ribosomes not be targeted in anti-viral medications?

A

viruses uses human ribosomes to replicate, meaning they would be attacked

32
Q

What is the central dogma?

A

a theory stating that genetic information flows only in one direction, from DNA, to RNA, to protein, or RNA directly to protein.

DNA -> RNA -> proteins

33
Q

Whose polymerase do viruses use to replicate?

A

Their own

34
Q

Why do viruses have a high mutation rate?

A

They use their own polymerase to replicate which LACK PROOF READING

35
Q

RNA is shorter than DNA. How do RNA viruses compensate for this?

A

They use COMPLEX CODING STRATEGIES to they can make more proteins than expected

36
Q

Why is it useful for DNA viruses to be large?

A

They have room to acquire accessory genes which could make that virus better at modifying host immune response

37
Q

What is a segmented genome and how does this impact viruses?

A

Allows easy recombination, therefore if different strains of the virus enter the host, reassortment can occurs, producing new variants

38
Q

What is the size range of viruses?

A

1nm to 1 micrometer

39
Q

What are two examples of neuramidase inhibitors?

A

Tamiflu and Relenza

40
Q

What is Remdisivir a nucleoside inhibitor of?

A

Adenosine

41
Q

How does Remdisivir work as a nucleoside inhibitor?

A

Acts as adenosine, and causes chain termination three nucleosides later, due to the chain twisting

42
Q

What is Remdisivir used to treat?

A

Hepatits C

43
Q

What is amantidine?

A

A adamantine

44
Q

How does amantidine work as an antiviral?

A

Blocks the M2 ion channel which would normally allow H+ ions to enter into the endosome, meaning that the virus is trapped inside the endosome and therefore cannot replicate

45
Q

Why is the use of amantidine not recomendable?

A

Most H3N2 viruses are resistant to it

46
Q

How do NA inhibitors work?

A

They block the action of neuramidase preventing the virus from being released from the cell
Normally, NA works by cleaving the sialic acid / HA binding which the virus does to latch into the host cell, allowing the virus to leave

47
Q

What are tamiflu and relenza used to treat?

A

Influenza

48
Q

What is the lipid envelopes of viruses derived from?

A

The host cell membrane

49
Q

What is the cell membrane of a non-enveloped virus made from?

A

Pure proteins

50
Q

In cultured cells, why are some genes in virus’ genome lost?

A

Some genes are used to limit the immune response of the host cell against the virus to give the virus an advantage, however there is no immune response in cultured cells therefore these genes are not needed

51
Q

What are the stages of viral replication?

A 
Attachment
Insertion
Translation
Assembly
Exocytosis
52
Q

What do direct acting antivirals target?

A

Specific viral factors

53
Q

What are biologicals?

A

Antibodies which are derived from recovered individuals or synthesized in the lab from immobilized B cells - given directly into the blood

54
Q

What anti-virals are used to treat Hepatitis C?

A

Direct Acting Antivirals

55
Q

Between Relenza and Tamiflu, which is more effective and why?

A

Tamiflu - the chemistry of relenza means the virus can more readily acquire resistance so less effective

56
Q

Acyclovir and ribavirin are both antiviral agents that act as nucleoside analogues. Why is acyclovir effective against herpes simplex virus but not influenza?

A

c) Because acyclovir is only converted to its active form inside a cell infected by herpes virus that encodes thymidine kinase, and influenza virus does not encode such an enzyme.

57
Q

Tamiflu (oseltamivir) is an antiviral drug that can be used to treat influenza virus infection. The mechanism of action is:

A

a) To inhibit the neuraminidase enzyme that removes sialic acid from the infected cells surface and allow onwards spread of new virus particles.

58
Q

Why might a patient with chronic hepatitis C virus treated with an HCV protease inhibitor drug show a loss of a positive viral response over time?

A

The virus has acquired resistance to the drug.

The patient has continued in high risk lifestyle and acquired a second infection with a different strain of HCV.

The patient has stopped taking the drug because it gave unpleasant side effects.

59
Q

Two people in the world are believed to have been ‘cured’ of HIV. How has this been achieved?

A

They have undergone bone marrow transplantation with cells from a CCR5 delta 32 donor.

60
Q

what is PrEP for HIV?

A

Pre exposure Prophylaxis (PrEP) means taking HIV antivirals daily to prevent possible HIV infection during sex with an infected partner.

61
Q

BHIVA guidelines require that people have an HIV test before going on PrEP. Why is this so important?

A

If the person is already HIV infected you don’t want to be giving them treatment with only two drugs as resistance can likely be selected more easily than the standard which is three drugs at once.

62
Q

Single use of antiviral agents increase the risk of resistance. How is this overcome?

A

Through the use of combination therapy - this means the chances of anti-viral resistance is much less likely, as the virus would have to have a gene mutation against every single drug in the combination

63
Q

What are four stages of HIV replication which are targeted in combination therapy?

A
  1. Viral entry inhibition
  2. Integration of viral genome inhibition
  3. Protease inhibition
  4. Reverse transcriptase inhibitors
64
Q

What are the consequences of viral genome type?

A
  • RNA viruses and retroviruses use their own polymerase to replicate. These lack proof-reading capacity leading to high mutation rate.
  • RNA viral genomes are limited in size due to inherent instability to RNA vs DNA. The largest RNA viruses are coronaviruses genome size around 30kb. RNA viruses often use complex coding strategies to make more proteins than expected from a small RNA genome.
  • DNA viruses have genomes up to 100s kb. There is plenty of room for accessory genes that can modify the host immune response. These genes are often lost in passage in culture.
  • Segmented genomes allow an additional easy form of recombination known as reassortment, but also impose more difficult packaging strategies. Influenza has 8 different RNA segments, rotavirus has 11.
65
Q

What is amantidine/ Rimantadine?

A

cyclic amines with bulky, cage like structures
By products of petroleum refinement
Active against influenza A virus only

66
Q

What are the three neuraminidase inhibitors?

A

Sialic acid
Relenza
Tamiflu

POM IMMUNOLOGY (13 decks)

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