Viral Evasion of the Host Immune Response

Question 1

What is a key difference between internal virus proteins and surface antigens?

Answer 1

Internal viral proteins vary less

Question 2

Describe the process of presentation of viral peptides on MHC Class I.

Answer 2

Viral peptides are chopped up by the proteasome  
These peptides are then fed through the TAP protein into the endoplasmic reticulum  
In the endoplasmic reticulum, it will be loaded onto an MHC class I molecule and it will then move to the cell surface where T cells can recognise the antigen

Question 3

State three viruses (and the proteins involved) that evade antigen loading onto TAP.

Answer 3

EBV – EBNA1 – this cannot be chopped up by the proteasome
HSV – ICP47 – blocks access of the peptides to the TAP protein
CMV – US6 – blocks ATP binding to TAP

Question 4

State two viruses (and the proteins involved) that modulate tapasin function and prevent MHC transport.

Answer 4

NOTE: tapasin is involved in loading MHC molecules
Adenovirus E3-19K – prevents recruitment of TAP to tapasin and retains MHC in the ER
CMV – US3 – binds to tapasin and prevents loading of peptides onto MHC

Question 5

State one virus (and the protein involved) that interferes with MHC presentation at the cell surface.

Answer 5

KSHV (Kaposi Sarcoma Herpes Virus) – kK3 – induces polyubiquitination and internalisation of MHC

Question 6

What do NK cells recognise on the cell surface that triggers killing of cells?

Answer 6

Missing self – lack of MHC on the cell membrane is not healthy

Question 7

How do viruses evade this mechanism of NK-mediated killing infected cells?

Answer 7

1. Viruses encode MHC analogues (e.g. CMV gp UL40) – virally encoded MHC is useless but it fools the NK cells
2. Upregulate MHC

Question 8

Which cells does HIV target?

Answer 8

CD4+ T cells

Question 9

Which cells does Ebola kill?

Answer 9

Dendritic cells
Macrophages
T cells (by the bystander response)

Question 10

In what subset of the population does HCMV (human cytomegalovirus) cause disease?

Answer 10

Immunocompromised. Once infected, the infection is lifelong but is controlled by the immune system. It is re activated when immune system becomes weak

Question 11

What is the problem with HCMV with regards to bone marrow transplantation?

Answer 11

HCMV infects 60-90% of the population

If HCMV is present in donated bone marrow, it could cause problems in the immunocompromised recipient

Question 12

What is antigenic drift?

Answer 12

Continued rapid evolution driven by antigenic pressure from the host

Question 13

What is antigenic shift?

Answer 13

Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.

Question 14

How else can viruses cause regular infections without changingtheir antigen profile?

Answer 14

They can have several genetically stable serotypes that co-circulate
E.g. rhinovirus has more than 120 antigenically distinct serotypes

Question 15

How many serotypes of influenza are there?

Answer 15

4

Question 16

How many serotypes of poliovirus are there and what type of vaccine was produced for polio?

Answer 16

3 – trivalent vaccine

NOTE: one of the serotypes has been eradicated now

Question 17

How many serotypes of dengue are there?

Answer 17

4

Question 18

Why do you need to be vaccinated against all 4 dengue serotypes instead of just one?

Answer 18

Antibody dependent enhancement:
Antibody generated against a previous infection (different serotype) can bind to the new serotype but NOT neutralize the virus. Fc receptors on monocytes can then bind to the Ab (bound to antigen). This leads to mass release of cytokines by monocytes (cytokine storm), causing Dengue Haemorrhagic Fever.

Question 19

What can viruses do to glycoprotein antigens that hinder antibody access to the antigens?

Answer 19

Heavily glycosylate the antigens

Question 20

What does Ebola viruse have a high content of that makes them appear like apoptotic bodies?

Answer 20

Phosphatidyl serine lipids

Question 21

What is the benefit to Ebola virus of appearing like apoptotic bodies?

Answer 21

They are rapidly taken up by macropinocytosis and, hence, taken away from antibody surveillance

Question 22

How does the structure of Ebola affect antibody access to antigens?

Answer 22

Ebola has a long filamentous shape with lots of folds

The folds may make the glycoproteins inaccessible to antibody

Question 23

Name two factors produced by Ebola that allow it to evade detection by the innate immune system.

Answer 23

VP35

VP24

Question 24

What important factor does Ebola encode that also helps deal with the antibody response?

Answer 24

Soluble glycoprotein – this acts as an antibody decoy and it is immunosuppressive (inhibits neutrophils)
NOTE: GP2 and retrovirus glycoproteins also have an immunosuppressive peptide

Question 25

Which virus is only suppressive in macaques?

Answer 25

Reston virus

Question 26

How does Measles infect cells?

Answer 26

Via SLAM proteins (CD150)

Question 27

Why did the measles vaccine have a much larger effect on childhood mortality than expected?

Answer 27

Measles can infect memory lymphocytes (these are SLAM positive) and erase immunological memory
So a measles virus infection can result in a 2-3 year decrease in immunological memory that leads to morbidity and mortality from otherdiseases