Viruses, Immune Evasion and HIV Flashcards
What is otitis media?
List 2 pathogens that cause it.
Where are these pathogens obtained from?
- An inflammatory disease of the ear.
- Caused by Haemophilus influenzae and Streptococcus pneumoniae (bacteria).
- These bacteria are part of the normal commensal flora.
How does otitis media arise?
Give an example of another infection that came about in the same way.
- 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.
What is the Red Queen hypothesis?
That organisms must constantly adapt, evolve, and proliferate in order to survive in a constantly changing environment.
What is the difference between antigenic shift and antigenic drift?
- 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.
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?
- Measles.
- It cannot tolerate mutations due to changing protein stability.
- Only one vaccination for measles is therefore necessary.
What is the difference between positive sense (group 4) and negative sense (group 5) rna?
- 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.
Why are negative-sense (group 5) RNA genomes more genetically diverse than positive-sense (group 4) RNA genomes?
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.
Which type of RNA genomes are more commonly segmented?
Why?
What is the advantage of segmentation?
- Negative- sense (group 5) RNA genomes.
- Because they generally encode more genetic information.
- Segmentation allows for reassortment of genetic information.
Which type of RNA viruses require RNA polymerase?
Why?
- Negative-sense (group 5) only.
- Because positive sense (group 4) RNA do not need to be transcribed before being translated.
Define ambisense.
Partly negative sense and partly positive sense.
Which type of RNA genomes are sometimes ambisense?
Negative sense (group 5).
- Debate over whether they should be part of a separate group.
Give an example of a virus that has an ambisense genome.
Lassa virus.
List 4 negative sense (group 5) RNA viruses.
1 - Ebola.
2 - Measles.
3 - Lassa.
4 - Influenza.
Briefly describe the organisation of the influenza virus genome.
- 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.
List 2 clinically important genes of the influenza virus.
1 - Gene 4: haemagglutinin (H or HA).
2 - Gene 6: neuraminidase (N or NA).
What is the receptor for human influenza?
What about bird and swine flu?
From which molecules are these receptors derived?
- 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.
What is amantadine?
What is its mechanism of action?
- An antiviral drug that was used to treat influenza.
- It works by binding to the M2 ion channel protein active site.
When did viral resistance to amantadine arise?
Which mutations conferred this resistance?
- In the 2005/2006 flu season.
- An S31N point mutation in the M2 ion channel protein.
What is original antigenic sin?
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.
What is superinfection?
Where 2 viruses mix in the same cell, causing a new infection being superimposed on an earlier one.
List 4 reasons for the difference between the evolution of measles and flu.
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.
Define serotype.
A group of organisms within a species that have the same type and number of surface antigens.
Define epitope.
The part of an antigen to which an antibody attaches.
Why does measles only have one serotype?
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.
How do retroviruses replicate?
- 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.
How much of the human DNA is ‘dead’ retrovirus DNA?
8%.
Describe the HIV life cycle.
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.
Where do type A, B and C retroviruses encapsidate?
- Type A and B encapsidate within the cell.
- Type C encapsidate at the plasma membrane.
What is the visual difference between the membranous spikes of type B, C and D retroviruses?
- B: Big spikes.
- C: Almost invisible spikes.
- D: Small spikes.
Give an example of a retrovirus for retrovirus types A, B, C and D.
- A: Human endogenous retrovirus (HERV).
- B: Mouse mammary tumour virus (MMTV).
- C: Human immunodeficiency virus (HIV).
- D: Mason pfizer monkey virus (MPMV).
List the components of the HIV genome.
1 - Core protein.
2 - Viral infectivity factor.
3 - Viral protein U.
4 - Envelope gene.
5 - Negative effector.
Which group of RNA viruses is the least variable?
RNA retroviruses.
List the phases of HIV infection.
1 - Acute phase.
2 - Symptom-free interval.
3 - AIDS-related complex.
4 - AIDS.
What is the life expectancy of a person with untreated HIV?
10-15 years.
What is the key step of HIV maturation?
Cleaving of p55 into p24 and p17 by protease.
List two types of HIV drugs.
1 - Protease inhibitors.
2 - Reverse transcriptase inhibitors.
List 3 advantages and 3 disadvantages to use of protease inhibitors and reverse transcriptase inhibitors.
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.
Define cross resistance.
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).
What is HAART?
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.
Give 2 examples of typical HAART combinations.
1 - 2 different nucleoside reverse transcriptase inhibitors + 1 non-nucleoside reverse transcriptase inhibitor.
2 - 2 different nucleoside reverse transcriptase inhibitor + 1 protease inhibitor.
What is the cause of the latent / symptom-free interval of HIV?
A stable reservoir of resting, inactive T cells which harbour transcriptionally latent HIV.
What is the mechanism of action for PGT121 in treatment of HIV?
- 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.
What is the mechanism of action for GS-9620 in treatment of HIV?
- 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.
Which group of people are usually infected by Herpesvirus gladitorum?
How is it transmitted?
Rugby players and sumo wrestlers through skin abrasion.
How many types of human herpesvirus are there?
8 types (HHV1-8).
Define zoonosis.
A disease which can be transmitted from animals to humans.
How do vaccines for varicella zoster virus work?
1 - Reactivation of latent infection.
2 - Suppression of cell-mediated immunity.
3 - Re-exposure of humoral response to the virus.
What type of genome does herpesvirus have?
Double stranded DNA.
What type of virus is hepatitis B?
DNA retrovirus.
List 2 types of herpesvirus.
1 - Epstein-Barr virus (EBV).
2 - Herpes simplex virus (HSV).
Which proteins are expressed by EBV and HSV that enable them to produce latent infection?
- 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.
