Viral evasion of the host immune response

Question 1

What are virus proteins easy targets for and why?

Answer 1

Their proteins are easy targets for processing and presentation by MHC because they are intracellular pathogens

Question 2

What clears viral infection?

Answer 2

Cellular immunity but its is short lived

Question 3

Why are internal viral proteins targets for cellular immunity?

Answer 3

As they are intracellular, they tend to vary less than surface antigens

Question 4

What must viruses evade to survive?

Answer 4

Cellular immunity

Question 5

What happens to foreign peptides inside a cell?

Answer 5

They will be chopped up into smaller peptides inside the proteasome

Question 6

What happens to the smaller peptides formed from the proteasome?

Answer 6

They get fed in through the TAP proteins into the endoplasmic reticulum where it gets loaded onto an MHC class I molecule

Question 7

What happens to the loaded MHC class I molecule?

Answer 7

It moves to the cell membrane where the viral peptide can be recognised by T cell receptors on the surface of cytotoxic T cells

Question 8

What does the T cell do upon recognising viral peptides?

Answer 8

Kills the virus infected cell

Question 9

How does EBV evade cellular immunity?

Answer 9

It expresses a protein called EBNA1 that cannot be cut into smaller peptides in the proteasome- so EBV can exist in the cell but its proteins are not processed

Question 10

How does HSV evade cellular immunity?

Answer 10

It encodes ICP47 which blocks access of processed peptide to TAP

Question 11

How does CMV evade cellular immunity?

Answer 11

It encodes US6 which stops ATP binding to TAP, which is required for TAP to be able to transport peptides across the membrane

Question 12

How does CMV prevent MHC transport?

Answer 12

It encodes US3 which binds to tapasin and prevents peptides being loaded onto MHC

Question 13

How does adenovirus E3-19K prevent MHC transport?

Answer 13

It prevents recruitment of TAP to tapasin and retains MHC in the ER

Question 14

How does Kaposi sarcoma herpes virus kK3 protein evade the immune system?

Answer 14

It induces polyubiquitination and internalisation of MHC so virus peptides won’t be presented to T cells

Question 15

What does the lack of MHC by a cell normally lead to?

Answer 15

Detection by NK cells and they are killed

Question 16

How do viruses that disrupt MHC presentation evade NK cells?

Answer 16

These viruses encode MHC analogues or up regulate MHC. The virally encoded MHC is useless and doesn’t trigger the immune response but it does fool the NK cells into thinking that cells are normal

Question 17

How does HIV evade cellular immunity?

Answer 17

It targets CD4+ T cells and depletes the ability to support an immune response

Question 18

How does ebola virus evade cellular immunity?

Answer 18

It results in destruction of target dendritic cells and macrophages by direction infection and of T cells by a bystander response

Question 19

What percentage of people are infected by HCMV and in who does it cause a problem?

Answer 19

80-90% are infected but it only causes a problem in people that are immunocompromised

Question 20

When does HCMV virus need to be eliminated from bone marrow cells?

Answer 20

Before transplantation because otherwise it will reactivate in an immunosuppressed transplant recipient

Question 21

What does UL138 protein produced by CMV infected cells lead to?

Answer 21

Loss of MRP-1 from infected cell surface

Question 22

What is MRP-1?

Answer 22

Transporter that transports toxic drugs out of cell

Question 23

What does loss of MRP-1 transporter lead to?

Answer 23

Accumulation of certain molecules in infected cells including the toxic drug vincristine

Question 24

How are cells from a donor treated before transplantation to eliminate CMV?

Answer 24

They can be vincristine treated- it has improved the outcome in the bone marrow transplant

Question 25

What is influenza antigenic drift?

Answer 25

Continued rapid evolution driven by antigenic pressure from the host

Question 26

What is influence antigenic shift?

Answer 26

Introduction of new subtypes from animal source

Question 27

What are serotypes?

Answer 27

Differently genetically stable forms of disease that can cocirculate in humans

Question 28

What is the result of the antigenic drift of influenza?

Answer 28

The influenza vaccine must be updated every year

Question 29

How many subtypes are there of influenza?

Answer 29

4

Question 30

How would a universal flu vaccine be developed?

Answer 30

Antibodies produced against parts of the spike proteins that are conserved

Question 31

How many serotypes are there of rhinovirus?

Answer 31

More than 120 antigenically distinct serotypes- impossible to make a vaccine against

Question 32

How many serotypes are there of poliovirus?

Answer 32

Three- requires a trivalent polio vaccine

Question 33

How does HIV evade antibodies?

Answer 33

The HIV env spike gp120 resists neutralisation because: Large space between spikes prevents Ab cross linking Extensive glycosylation masks antibody epitopes Functionally important parts of the molecule are poorly accessible

Question 34

What is the consequence of antigenic variation in dengue virus?

Answer 34

Dengue haemorrhagic fever is responsible for a lot of hospitalisation and fatalities- it causes leakage of plasma from capillaries and this loss of fluid leads to increased haematocrit and increased red cell count and decrease in protein in blood. There is a tendency to severe bruising and bleeding. Patient deteriorates even after the fever drops It is treated with IV fluids

Question 35

How many serotypes of dengue are there?

Answer 35

Four

Question 36

How do antibodies enhance dengue?

Answer 36

Antibody generated against a previous dengue infection can bind to but not neutralise the current dengue infection. It can lead to antigen dependent enhancement (ADE) causing Dengue Haemorrhagic Fever

Question 37

How do some viruses evade the antibody response?

Answer 37

They have glycoprotein antigens that are so heavily glycosylated that antibody access is hindered e.g. HIV and ebola (looks more like human mucin because they are so glycosylated)

Question 38

How does ebola virus evade the antibody response?

Answer 38

Their particle membranes have a high content of phosphatidyl serine lipids making them look like apoptotic bodies. As they look like apoptotic bodies, they are rapidly taken up macropinocytosis, away from antibody surveillance. It also has a long filamentous shape which has lots of folds so glycoproteins may be inaccessible in these viral pockets making it harder for antibodies to neutralise the glycoprotein.

Question 39

How does VP35 and VP24 help ebola?

Answer 39

It stops the innate immune response from seeing ebola

Question 40

What does ebola synthesis to act as an antibody decoy?

Answer 40

Soluble glycoproteins- it is the default coding for the glycoprotein gene, it is also immunosuppressive and inhibits neutrophils

Question 41

How effective was measles vaccination and why?

Answer 41

It had a much larger effect than expected on childhood mortality. Measles infects CD150 (SLAM) positive cells, which includes memory lymphocytes and erases immunological memory, so meals virus infection can result in 2-3 yr decrease in immunological memory that leads to morbidity and mortality from other diseases