Viral evasion of host immunity

Question 1

Evasion of antigen loading to TAP

Answer 1

• EBV EBNA1 cannot be processed by the proteasome
• HSV ICP47 blocks access of processed peptide to TAP
• CMV US6 stops ATP binding to TAP preventing translocation

Question 2

Modulation of tapasin function and prevention of MHC transport

Answer 2

• CMV US3 binds tapasin and prevent peptides being loaded to MHC
• Adenovirus E3-19K prevents TAP recruitment to tapasin and also retains MHC in the endoplasmic reticulum

Question 3

Interfering with MHC presentation at the cell surface

Answer 3

• KSHV kK3 protein induces polyubiquitinlyation and internalisation of MHC
• From the internalised endosome, MHC is passed to lysosomes where it is degraded

Question 4

NK killing avoidance

Answer 4

MISSING SELF MECHANISM

• normal health cells display MHC at their surface
• cells that don’t display MHC are detected by natural killer cells and killed
• viruses that disrupt MHC presentation would end up being killed by natural killer cells
• viruses encode MHC analogues or upregulate MHC

Question 5

Haemagglutinin

Answer 5

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Question 6

Strategies to stimulate bnAb production

Answer 6

Skewing the antibody response towards the HA2 stalk region via:

• headless HA
• hyperglycosylating HA1 head domain
• peptides against fusion peptide (FP) and ectodomain (EHA2)

Question 7

Antibody evasion by HIV

Answer 7

HIV env spike gp120 resists neutralisation because:

• large space between spikes prevents antibody crosslinking
• extensive glycosylation masks antibody epitopes
• functionally important parts of the molecule are poorly accessible, CD4 binding site, redundant amino acids are visible to B cell receptor and antibodies
• huge variation in the redundant amino acids means most antibodies are highly clade specific

Question 8

Serotypes of the human rhinovirus

Answer 8

• human rhinoviruses cause the common cold
• exist as more than 120 antigenically distinct serotypes that co-circulate
• impossible to make vaccine against all serotypes

Question 9

Poliovirus

Answer 9

• three serotypes required a trivalent poliovirus vaccine
• for live attenuated Sabin vaccine, admin of all 3 at once resulted in virus interference and poor response to one component
• one serotype has been eradicated from the world

Question 10

Antigenic variation consequences of Dengue virus

Answer 10

DENGUE HAEMORRHAGIC FEVER

• responsible for 500,000 hospitalisations each year with 5% fatalities
• leakage of blood plasma from capillaries
• detected by increase in RBC and decrease in blood protein level
• tendency to severe bruising and bleeding
• patient deteriorates even after fever drops with shock
• treat with I.V. fluid replacement

Question 11

Antibody dependent enhancement of Dengue virus

Answer 11

• Dengue virus exists as 4 different serotypes
• antibody generated against a previous infection can bind but not neutralise, and lead to ADE, causing Dengue Haemorrhagic Fever

Question 12

Virus-mediated immunosuppression

Answer 12

• measles vaccination=much larger impact on childhood mortality than expected if it only protected against measles virus itself
• MV (measles virus) infects CD150 positive cells (including memory lymphocytes) and erases immunological memory
• MV (measles virus) infection results in 2-3 year decrease in immunological memory that leads to morbidity and mortality from other diseases

Question 13

Antigenic variation

Answer 13

• continued rapid evolution driven by antigenic pressure from host (influenza antigenic drift, HIV quasispecies)
• introduction of new subtypes from animal source (influenza antigenic shift)
• existing as different genetically stable serotypes that cocirculate in humans (eg: rhinovirus, poliovirus and Dengue)
• consequence for vaccination