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IIH > Viruses, Immune Evasion and HIV > Flashcards

Viruses, Immune Evasion and HIV Flashcards

1
Q

What is otitis media?

List 2 pathogens that cause it.

Where are these pathogens obtained from?

A
  • An inflammatory disease of the ear.
  • Caused by Haemophilus influenzae and Streptococcus pneumoniae (bacteria).
  • These bacteria are part of the normal commensal flora.
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2
Q

How does otitis media arise?

Give an example of another infection that came about in the same way.

A
  • Viral infections of the nasopharynx can lead to inflammation.
  • This promotes the conditions in which bacteria of the normal commensal flora thrive.
  • Another example is the Spanish flu, where influenza caused Streptococcus pneumoniae to cause bacterial pneumonia.
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3
Q

What is the Red Queen hypothesis?

A

That organisms must constantly adapt, evolve, and proliferate in order to survive in a constantly changing environment.

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4
Q

What is the difference between antigenic shift and antigenic drift?

A
  • Antigenic shift is the process by which two or more different strains of a virus combine to form a new subtype having a mixture of the surface antigens of the original strains.
  • Antigenic drift involves the accumulation of mutations within the genes that code for antigens.
  • Shift is more sudden than drift.
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5
Q

Give an example of a pathogen that does not undergo antigenic shift / drift.

Why is this pathogen unable to do so?

What is the clinical consequence of this?

A
  • Measles.
  • It cannot tolerate mutations due to changing protein stability.
  • Only one vaccination for measles is therefore necessary.
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6
Q

What is the difference between positive sense (group 4) and negative sense (group 5) rna?

A
  • Positive sense (group 4) is 5’ to 3’, and therefore does not need to be converted into mRNA.
  • Negative sense (group 5) is 3’ to 5’, and is complementary to the viral mRNA.
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7
Q

Why are negative-sense (group 5) RNA genomes more genetically diverse than positive-sense (group 4) RNA genomes?

A

Because of the difficulties of expression, positive-sense (group 4) RNA genomes tend to have smaller genomes than negative-sense (group 5) RNA genomes, and therefore encode less genetic information.

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8
Q

Which type of RNA genomes are more commonly segmented?

Why?

What is the advantage of segmentation?

A
  • Negative- sense (group 5) RNA genomes.
  • Because they generally encode more genetic information.
  • Segmentation allows for reassortment of genetic information.
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9
Q

Which type of RNA viruses require RNA polymerase?

Why?

A
  • Negative-sense (group 5) only.

- Because positive sense (group 4) RNA do not need to be transcribed before being translated.

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10
Q

Define ambisense.

A

Partly negative sense and partly positive sense.

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11
Q

Which type of RNA genomes are sometimes ambisense?

A

Negative sense (group 5).

  • Debate over whether they should be part of a separate group.
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12
Q

Give an example of a virus that has an ambisense genome.

A

Lassa virus.

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13
Q

List 4 negative sense (group 5) RNA viruses.

A

1 - Ebola.

2 - Measles.

3 - Lassa.

4 - Influenza.

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14
Q

Briefly describe the organisation of the influenza virus genome.

A
  • Contains 7 or 8 RNA segments that are numbered by size.
  • Segments 1 - 6 encode 1 protein each.
  • Segments 7 and 8 encode 2 proteins each.
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15
Q

List 2 clinically important genes of the influenza virus.

A

1 - Gene 4: haemagglutinin (H or HA).

2 - Gene 6: neuraminidase (N or NA).

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16
Q

What is the receptor for human influenza?

What about bird and swine flu?

From which molecules are these receptors derived?

A
  • Human influenza has 2-6 sialic acid.
  • Bird flu has 2-3 sialic acid.
  • Swine flu has both 2-3 and 2-6 sialic acid.
  • These are derivatives of neuraminic acid.
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17
Q

What is amantadine?

What is its mechanism of action?

A
  • An antiviral drug that was used to treat influenza.

- It works by binding to the M2 ion channel protein active site.

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18
Q

When did viral resistance to amantadine arise?

Which mutations conferred this resistance?

A
  • In the 2005/2006 flu season.

- An S31N point mutation in the M2 ion channel protein.

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19
Q

What is original antigenic sin?

A

The tendency of the body’s immune system to preferentially utilise immunological memory based on a previous infection rather than a new primary response when a second slightly different version of that pathogen is encountered.

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20
Q

What is superinfection?

A

Where 2 viruses mix in the same cell, causing a new infection being superimposed on an earlier one.

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21
Q

List 4 reasons for the difference between the evolution of measles and flu.

A

1 - Flu has a number of non-human hosts which can act as reservoirs of genetic material.

2 - Flu has a segmented genome whereas measles is not.

3 - Flu superinfection is common, increasing reassortment. Measles cannot reassort.

4 - Flu has more diverse serotypes, so is less readily neutralised than measles, which only has one strain.

22
Q

Define serotype.

A

A group of organisms within a species that have the same type and number of surface antigens.

23
Q

Define epitope.

A

The part of an antigen to which an antibody attaches.

24
Q

Why does measles only have one serotype?

A

Because its epitope overlaps with the virus binding site for the CD150 receptor (a glycogen antigen expressed on immune cells). This is too important to change.

25
Q

How do retroviruses replicate?

A
  • The RNA genome of retroviruses forms a template for reverse transcription into DNA rather than for translation.
  • The DNA is then incorporated into the host cell genome, which is transcribed as normal DNA.
26
Q

How much of the human DNA is ‘dead’ retrovirus DNA?

A

8%.

27
Q

Describe the HIV life cycle.

A

1 - Binding to CD4 on the host cell surface.

2 - Disassembly.

3 - Reverse transcriptase transforms RNA into DNA.

4 - Integrase incorporates viral DNA into the host cell genome.

5 - Production of viral RNA and proteins.

6 - Reassembly and encapsidation of original and new viruses.

7 - Release by budding of virus particles from the host cell membrane.

28
Q

Where do type A, B and C retroviruses encapsidate?

A
  • Type A and B encapsidate within the cell.

- Type C encapsidate at the plasma membrane.

29
Q

What is the visual difference between the membranous spikes of type B, C and D retroviruses?

A
  • B: Big spikes.
  • C: Almost invisible spikes.
  • D: Small spikes.
30
Q

Give an example of a retrovirus for retrovirus types A, B, C and D.

A
  • A: Human endogenous retrovirus (HERV).
  • B: Mouse mammary tumour virus (MMTV).
  • C: Human immunodeficiency virus (HIV).
  • D: Mason pfizer monkey virus (MPMV).
31
Q

List the components of the HIV genome.

A

1 - Core protein.

2 - Viral infectivity factor.

3 - Viral protein U.

4 - Envelope gene.

5 - Negative effector.

32
Q

Which group of RNA viruses is the least variable?

A

RNA retroviruses.

33
Q

List the phases of HIV infection.

A

1 - Acute phase.

2 - Symptom-free interval.

3 - AIDS-related complex.

4 - AIDS.

34
Q

What is the life expectancy of a person with untreated HIV?

A

10-15 years.

35
Q

What is the key step of HIV maturation?

A

Cleaving of p55 into p24 and p17 by protease.

36
Q

List two types of HIV drugs.

A

1 - Protease inhibitors.

2 - Reverse transcriptase inhibitors.

37
Q

List 3 advantages and 3 disadvantages to use of protease inhibitors and reverse transcriptase inhibitors.

A

Advantages:

1 - Highly specific, therefore safe.

2 - Defined specificity.

3 - Relatively fast to develop.

Disadvantages:

1 - Highly specific, therefore limited utility for different viruses.

2 - Defined specificity, therefore resistance mutations occur rapidly.

3 - Relatively expensive to manufacture.

38
Q

Define cross resistance.

A

The tolerance to a usually toxic substance (e.g. an antibiotic) as a result of exposure to a similarly acting substance (e.g. a different antibiotic).

39
Q

What is HAART?

A

The combination of multiple drugs as a therapy for HIV infection, where 3 or more drugs with distinct resistance profiles and differing target genes are co-administered.

40
Q

Give 2 examples of typical HAART combinations.

A

1 - 2 different nucleoside reverse transcriptase inhibitors + 1 non-nucleoside reverse transcriptase inhibitor.

2 - 2 different nucleoside reverse transcriptase inhibitor + 1 protease inhibitor.

41
Q

What is the cause of the latent / symptom-free interval of HIV?

A

A stable reservoir of resting, inactive T cells which harbour transcriptionally latent HIV.

42
Q

What is the mechanism of action for PGT121 in treatment of HIV?

A
  • PGT121 is an antibody which recognises and binds to HIV proteins on the surface of infected cells, triggering other immune cells to kill the cell.
  • Particularly useful in the latent / symptom-free phase of infection.
43
Q

What is the mechanism of action for GS-9620 in treatment of HIV?

A
  • GS-9620 activates inactive T cells which harbour transcriptionally latent HIV via the toll-like receptor 7 (TLR7) protein.
  • Activated T cells can be targeted by other immune cells to kill the cell.
44
Q

Which group of people are usually infected by Herpesvirus gladitorum?

How is it transmitted?

A

Rugby players and sumo wrestlers through skin abrasion.

45
Q

How many types of human herpesvirus are there?

A

8 types (HHV1-8).

46
Q

Define zoonosis.

A

A disease which can be transmitted from animals to humans.

47
Q

How do vaccines for varicella zoster virus work?

A

1 - Reactivation of latent infection.

2 - Suppression of cell-mediated immunity.

3 - Re-exposure of humoral response to the virus.

48
Q

What type of genome does herpesvirus have?

A

Double stranded DNA.

49
Q

What type of virus is hepatitis B?

A

DNA retrovirus.

50
Q

List 2 types of herpesvirus.

A

1 - Epstein-Barr virus (EBV).

2 - Herpes simplex virus (HSV).

51
Q

Which proteins are expressed by EBV and HSV that enable them to produce latent infection?

A
  • EBV: Expresses Epstein–Barr virus nuclear antigen.
  • HSV: Expresses latency associated transcripts, which are mRNAs which are processed into small interfering RNA (siRNA) which control the host cell.

IIH (26 decks)

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