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Describe the structure of picornaviruses
- hydrophobic continous binding groove
- VP1, VP2 and VP3 on the icosahedral paticle
- VP4 associated with the RNA
How does polyprotein processing occur in picornaviruses?
- 3C protease
- P1 cleaves itself, 3C cleaves itself and the rest
What vaccine is there for HAV?
inactivated
What vaccine is there for rhinovirus?
inactivated
What vaccines are there for poliovirus?
- IPV
- OPV
- OPV type 2
- sabin vaccine - blind - IRES and structural
What vaccine is there for Dengue recently available?
attenuated recombinant only in those previously infected
What is the immune response to RSV?
- bB cells produce neutralising antibodies against F + G that wanes over time
- T cell response more focused on clearance than protection
What causes symptoms in RSV?
- virus damaging cells
- build up of cellular debris, infiltration of immune cells and factors can block airways especially in those w small airways like infants
What vaccine was there for RSV?
- formaline
- worsened infections
- non-neutralising antibodies
- not fully understood - inbalanced T cell response
What antivirals are there for RSV?
- nucleoside analogues
- increase mutation rate and decrease viral mRNA production
- not fully understood
- looking into targeting polymerase directly
What are the roles of HPV genes?
- E1+E2 = viral gene expression
- E3 + E8 = putative
- E4 + E5 = genome amplification
- E6 + E7 = entry - immortalising cells
- L1 + L2 = capsid formatoin in upper epithelium
- LCR = regulatory squences
What can HPV cooperate with to cause cancer?
ras oncogenes
What is a new vaccine target for HPV?
- L1 outer capsid
- sucess in dogs
How can HPV persist?
- low copy number episomes
- E5, E6 and E7 immune evasion roles
- viral gene expression if shut off in the presence of infiltrating lymphocytes but viral episomes are not fully cleared frrom the basal cell layer
How does HCV enter cells?
- clathrin-mediated endocytosis
- through tight junctions
- can be due to binding to lipids and using LDL receptors
- or E1, E2 binding cell surface
Why does HCV only infect liver cells?
liver cells have specific miRNA on their 5’ ends of the genome that HCV requires
How can genetics affect HCV risk of chronic infection?
- SNPs in some genes
- IL28B gene associated with spontaneous and drug induced clearance
- CC protective TT conducive
What is the rates of HVC?
- 1% worldwide
- 0.3% UK
- 11% Egypt - shared needles in vaccination programme
What is the role of the polymerase of spanish influenza?
- produces mini viral RNAs
- activate RIG-1 which activates NFkB
- cytokine storm and innate immune response
What vaccine is actually used in influeza
- live attenuated with mutations in pol and NP similar to the classic split vaccine killed by detergents
What are some potential future targets for influenza vaccination?
- interfering particles
- M2e domain