Micro 3 - Viral evasion of host immunity

Question 1

internal viral proteins can be targets of cellular immunity. They tend to vary …. than surface antigens

Answer 1

Less than

Question 2

Every cell in the body has

Answer 2

MHC Class 1.

Viral and cellular peptides chopped up (by proteasome) and presented here (via ER and TAP protein)- they bind to T cell receptors on T Lymphocytes

Question 3

Cellular immunity clears viruses, but is short lived. Certain persistent viruses must evade cellular immunity, e.g. herpes.

Answer 3

Yah

Question 4

Viruses have evolved ways to prevent antigen presentation by MHC (1). Give examples

Answer 4

(before reading, remember TAP proteins on ER membrane move viral peptides into ER)

1. HSV (ICP47) - blocks access of processed peptide to TAP
2. CMV (cytomegalovirus - US6) - stops ATP binding to TAP so no translocation occurs into the ER
3. EBV (EBNA1) - cannot be processed by proteasome

Question 5

How can viruses modulate tapasin function and prevent MHC transport

Answer 5

e. g.
1. CMV US3 binds tapasin - prevents peptides being loaded onto MHC
2. Adenovirus E3-19K prevents recruitment of TAP to tapasin and also retains MHC in ER

Question 6

Name a virus that interferes with MHC presentation at the cell surface

Answer 6

KSHV (Kaposis Sarcoma)HV

Its kK3 protein induces polyubiquitinylation and internalisation of MHC —> from the internalised endoscope, MHC passed to lysosomes where it is degraded

Question 7

HPV encounters both innate and cellular immune response. What does it produce to evade

Answer 7

Innate immunity:

E6 - binds to TYK2 and IRF3

E7 - binds to IRF9 and STING

Cellular immunity:

E5 and E7

Question 8

How do viruses avoid being killed by NKs with a missing self?

Answer 8

Viruses encode MHC analogues(CMV gpUL40) or up regulate MHC.

NK cells kill cells without MHC presentation

Question 9

Antigenic variation is one way in which viruses have evolved. Give examples of serotypes that circulate in humans

Answer 9

HIV - develops into a quasispecies

Rhinovirus - 100s of serotypes

Poliovirus - 3 serotypes

Dengue - 4 serotypes

Question 10

What is the major influenza viral antigen

Answer 10

Haemaglutinnin

Question 11

How does HIV evade antibodies

Answer 11

HIV spike GP120 resists neutralisation because:

1. Large space between spikes - prevents Antibody crosslinking
2. Extensive glycosylation - masks antibody epitopes
3. Functionally important parts of molecule are poorly accessible (CD4 binding site). Decoy amino acids available to BCR and antibodies
4. Huge variation in redundant amino acids (decoys) - means most antibodies are highly clade specific

Question 12

What type of vaccine do we have against HIV?

Answer 12

Broadly-neutralising HIV antibody - works on constant region (bind GP120) that cross react with many HIV strains.

Problem with broadly neutralising is that, whilst it may control viral load, viruses can mutate - then survive and expand

Question 13

Which viruses cause the common cold

Answer 13

Human rhinoviruses

Question 14

Poliovirus has 3 serotypes so

Answer 14

The vaccine is trivalent

But different ratio of each serotype (so one isn’t dominant, etc)

One serotype has been eradicated from the world –> were in the endgame now

Question 15

If you get dengue (4 serotypes) a second time, what can happen

Answer 15

Dengue haemorrhagic fever - leakage of blood plasma from capillaries

Detected by increase in RBC and decrease in protein level in blood

Tendency to bruise and bleed severely. Treated with IV fluid replacement.

All due to antigenic variation of dengue virus

Question 16

Describe Antibody Dependent enhancement (ADE) of dengue

Answer 16

1. Person infected with a serotype of dengue (e.g. serotype 1)
2. Mild dengue response - antibodies to serotype 1 made
3. New infection of dengue (serotype 2), previous antibodies can bind to new virus serotype, but NOT neutralise (as different serotype).
4. Antibody (bound) recognised by monocyte and binds to monocyte via Fc portion –> virus (serotype 2) now has a new type of cell it can infect, and compromised immunity.
5. Viral load increases, dengue haemorrhagic fever

Question 17

Give an example of virus-mediated immunosuppression

Answer 17

Measles.

It infects CD150+ cells (e.g. memory Lymphocytes) —> erases immunological memory —> immunocompromised, so morbidity and mortality from other diseases as weaker immune system

Measles only has 1 serotype, definitely vaccinate

Question 18

Ebola virus makes soluble sGPs. What do these do

Answer 18

These are antibody decoys –> they mop up antibody and prevent the antibody from neutralising the actual virus. sGP is also immunosuppressive (inhibits neutrophils)

Question 19

Which type of viruses are more likely to have error-prone polymerases that promote antigenic variation?

Answer 19

RNA > DNA

Question 20

How do viruses counteract activation of innate immune system?

Answer 20

They encode proteins that cleave or target host immune factors for degradation

Question 21

What virus encodes a protein, “vif”, that counteracts APOBEC (IFN stimulated gene)

Answer 21

HIV - vif prevents APOBEC from inducing hypermutation of viral genome

Question 22

In Hep C virus, which protease cleaves MAVS and prevents activation of IFN

Answer 22

NS3/4A

Question 23

Genetic polymorphisms in what result in non-responsiveness to IFN treatmetn

Answer 23

IL-28b