E-module: Viral Immune Evasion Strategies

Question 1

How do antibodies neutralise extracellular virus?

Answer 1

• blocks viral attachment proteins (e.g. glycoproteins, capsid proteins)
• destabilises viral structure

Question 2

How do antibodies fight viral infections?

Answer 2

• neutralise extracellular virus
• opsonizes virus for phagocytosis
• promotes killing of target cell by complement cascade and antibody-dependent cellular cytotoxicity
• resolves lytic viral infections
• blocks viremic spread to target tissue

Question 3

What antibody is an indicator of recent or current viral infection?

Answer 3

IgM

Question 4

Is IgG or IgM a more effective antiviral?

Answer 4

IgG

Question 5

What is secretory IgA important for?

Answer 5

protecting mucosal surfaces

Question 6

What does resolution of a viral infection require?

Answer 6

• elimination of free virus (antibody agglutination)

- elimination of virus-producing cell (viral or immune cell-mediated lysis)

Question 7

Name some examples of viruses that can escape antibody recognition.

Answer 7

• human rhinoviruses (100s of antigenically distinct serotypes)
• HIV (multiple quasi-species)
• Hep B (HBV) and Ebola (encode secreted surface antigens that take in antibodies to stop it reaching viral particles or infected cells)
• Dengue virus (4 serotypes-infection w/1 them followed by another can lead to enhancement of disease as virus enters immune cells via antibody and Fc receptor)
• Influenza virus (antigenic drift and shift, constantly mutating and evolving)

Question 8

What consequences does viruses being able to evade antibody recognition have?

Answer 8

• too many serotypes make finding vaccine difficult

- vaccines have to reflect circulating virus types

Question 9

What proteins do virally infected cells produce?

Answer 9

Interferons (IFN)

Question 10

How is interferon induced?

Answer 10

By molecules made by viruses that are sensed by the cell as foreign or in the wrong cellular location e.g. double-stranded RNA, RNA that lacks a 5’ cap or DNA in cytoplasm

Question 11

What happens when interferon is secreted from an infected cell?

Answer 11

It binds to interferon receptors

IFN initiates antiviral state in infected cells and in surrounding cells

Question 12

What does the antiviral state involve?

Answer 12

Transcription of hundreds of genes that block viral replication e.g. 2’5’ oligoadenylate synthetase and protein kinase R

Question 13

What does interferon activate?

Answer 13

Natural killer cells and systemic antiviral responses

Question 14

What are Type I IFNs?

Answer 14

IFN-alpha and IFN-beta

Question 15

What cells secrete IFN-beta?

Answer 15

All cells

Question 16

The IFN-alphaR receptor is present on what tissues

Answer 16

All tissues

Question 17

What type of cells are specialist IFN-alpha secreting cells?

Answer 17

Plasmacytoid dendritic cells (PDCs)

Question 18

How many genes are there for IFN-beta?

Answer 18

one

Question 19

How many isotypes are there for IFN-alpha?

Answer 19

13/14 isotypes

Question 20

What is Type II IFN?

Answer 20

IFN-gamma

Question 21

What is type II IFN produced by?

Answer 21

Activated T cells and NK cells

Question 22

What receptor does type II IFN signal through?

Answer 22

IFN-gammaR

Question 23

What is Type 3 interferon?

Answer 23

IFN - gamma that signals through receptors IL28R and IL10-B a.k.a IFN gamma receptors that are mainly present on epithelial surfaces

Question 24

What can viruses like hep B and influenza do?

Answer 24

Block production of IFN by inhibition of IFN transcription (HBV) or influenza virus produced a protein (NS1) that counters RNA sensing and prevents polyA processing

Question 25

What are NK cells activated by?

Answer 25

IFN-alpha and interleukin-12

Question 26

What do NK cells activate macrophages with?

Answer 26

IFN-gamma

Question 27

What do NK cells do?

Answer 27

Target and kill virus-infected cells (especially enveloped viruses)

Question 28

What happens when the NK cell finds a cell displaying fewer than normal MHC molecules?

Answer 28

It releases toxic substances, in a similar way to cytotoxic T cells - kills virally infected cell

Question 29

What do macrophages do?

Answer 29

• Filter viral particles from blood

- Inactivate opsonised virus particles

Question 30

What do immature and plasmacytoid DCs produce?

Answer 30

IFN-alpha and other cytokines

Question 31

What do DCs initiate/determine?

Answer 31

Nature of CD4 and CD8 T cell response

Question 32

What do both DCs and macrophages present?

Answer 32

Antigens to CD4 T Cells

Question 33

What are T cells essential for?

Answer 33

Controlling enveloped and nocytolytic viral infections

Question 34

What do T cells recognise?

Answer 34

Viral peptides presented by MHC molecules on cell surfaces

Question 35

Where can antigenic viral peptides (linear epitopes) come from?

Answer 35

Any viral protein (e.g. glycoproteins, nucleoproteins)

Question 36

What do CD8 cytotoxic T cells respond to?

Answer 36

viral peptide: class I MHC protein complexes on infected cells surface

Question 37

How can CD4 Th2 responses be detrimental?

Answer 37

If they prematurely limit the Th1 inflammatory and cytolytic responses

Question 38

How do viruses that result in chronic infections counter the T cell response?

Answer 38

Large DNA viruses like herpes simplex (HSV) and cytomegalovirus (CMV) encode proteins that interfere w/ MHC antigen processing pathway

Question 39

How can viruses impair lymphocyte function?

Answer 39

• HIV kills CD4 T cells and alters macrophage function

- Herpes simplex virus can prevent CD8 T-cell killing

Question 40

Summarise the main ways viruses evade the immune response.

Answer 40

• VIPRS: viral proteins that interfere with antigen presentation
• Disarm innate immunity
• Regulate MHC molecules
• Alter antigen presentation
• Interfere with CTL and NK cells
• Go into latency