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(54 cards)
1
Q
Describe the structure of picornaviruses
A
- hydrophobic continous binding groove
- VP1, VP2 and VP3 on the icosahedral paticle
- VP4 associated with the RNA
2
Q
How does polyprotein processing occur in picornaviruses?
A
- 3C protease
- P1 cleaves itself, 3C cleaves itself and the rest
3
Q
What vaccine is there for HAV?
A
inactivated
4
Q
What vaccine is there for rhinovirus?
A
inactivated
5
Q
What vaccines are there for poliovirus?
A
- IPV
- OPV
- OPV type 2
- sabin vaccine - blind - IRES and structural
6
Q
What vaccine is there for Dengue recently available?
A
attenuated recombinant only in those previously infected
7
Q
What is the immune response to RSV?
A
- bB cells produce neutralising antibodies against F + G that wanes over time
- T cell response more focused on clearance than protection
8
Q
What causes symptoms in RSV?
A
- 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
9
Q
What vaccine was there for RSV?
A
- formaline
- worsened infections
- non-neutralising antibodies
- not fully understood - inbalanced T cell response
10
Q
What antivirals are there for RSV?
A
- nucleoside analogues
- increase mutation rate and decrease viral mRNA production
- not fully understood
- looking into targeting polymerase directly
11
Q
What are the roles of HPV genes?
A
- 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
12
Q
What can HPV cooperate with to cause cancer?
A
ras oncogenes
13
Q
What is a new vaccine target for HPV?
A
- L1 outer capsid
- sucess in dogs
14
Q
How can HPV persist?
A
- 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
15
Q
How does HCV enter cells?
A
- clathrin-mediated endocytosis
- through tight junctions
- can be due to binding to lipids and using LDL receptors
- or E1, E2 binding cell surface
16
Q
Why does HCV only infect liver cells?
A
liver cells have specific miRNA on their 5’ ends of the genome that HCV requires
17
Q
How can genetics affect HCV risk of chronic infection?
A
- SNPs in some genes
- IL28B gene associated with spontaneous and drug induced clearance
- CC protective TT conducive
18
Q
What is the rates of HVC?
A
- 1% worldwide
- 0.3% UK
- 11% Egypt - shared needles in vaccination programme
19
Q
What is the role of the polymerase of spanish influenza?
A
- produces mini viral RNAs
- activate RIG-1 which activates NFkB
- cytokine storm and innate immune response
20
Q
What vaccine is actually used in influeza
A
- live attenuated with mutations in pol and NP similar to the classic split vaccine killed by detergents
21
Q
What are some potential future targets for influenza vaccination?
A
- interfering particles
- M2e domain
22
Q
How does RSV evade the host innate immune response?
A
- NS1+2 subvert interferon signalling and production
- methylation by host machinery hides it
- delaying the innate immune response allows more disease progression
23
Q
How does coronavirus make accesory proteins?
A
- from subgeomic RNA produced by discontinous transcription
- replication translation complex reaches specific TRS elements in the DNA that make it jump to the 5’ end and encode sgRNA - sgmRNA - accessory proteins
24
Q
How does coronavirus evade the immune response (6) ?
A
- NSP1 inhibits translation of IFNs
- inhibit PKR
- inhibit NKs
- inhibit inflammasomes
- structural proteins can interfere with host machinery
- accessory proteins
25
What kinds of proteins does coronavirus produce? name 7 important ones
- helicase
- polymerase
- endo/exonucleases
- RNA capping enzymes
- NSP1 shuts off host translation
- NSP3 + 4 involved in making double membranes vesicles derived from the ER
- accessory proteins
26
How is calicivirus replicated?
- ssRNA is made into antigenome as templates for progeny or for subgenomic RNA
- this can be translated into viral proteins
- accumulation of the major coat protein causes self assembly as accumulation of just this in culture - VLPs
27
How does calicivirus evade the innate immune response?
- NS1 + vpg involved
- NS3 inhibits ISGs
- inhibit STAT1 and IFN-B
- shut off host translation
28
Are there calcirivus antivirals?
drugs targeting the human protein HSP90 that interacts with viral vpg and RNA could reduce the rates of drug resistance
29
How does rotavirus mature?
- moves through the ER after replication
- gains a transient envelope on its way through that it then loses before leaving the cell by lysis
30
What vaccination is available for rotavirus?
- live attenuated from one strain
- live reassorted bovine-human pentavalent vaccine
- tried a tetravalent vaccine from rhesus monkeys that caused intasussception
31
How is Filovirus sGP made?
- 70% normal transcription and sGP
- 20% polymerase adds an extra A and changes the reading frame to GP
32
How does Ebola evade the immune response?
- VP24 and VP35 most important
- can stop STAT1 from entering the nucleus and activating IFNs and ISGs
- can interact with IFITMs to stop them from preventing virus entry
- G2 can interact with tertherin to stop it preventing virus exit
33
Are there antivirals for Ebola?
- no
- humanised neutralising Ab cocktails focused on the GP protein can be used
34
Describe Ebola virus vaccination
- focuses on neutralising Abs against GP
- no sGP
- adenovirus recombinant most frequently used
35
Which virus replicates by rolling circle?
herpesvirus
36
Which virus has 1 partial strand and 1 complete strand?
HBV
37
What are the current vaccines in trials for EBV?
- 2 in phase 1
- mRNA vaccine that targets glycoproteins on the virus particle
- nanoparticle vaccine that targets surface protein gp350 on the virus and on virus infected cells
38
What can HBV produce that can act as decoys to the immune system/
subviral particles with no genome or capsid that can misdirect antivody and completement responses
39
how does EBV enter cells?
with the use of the gH/gL complex, an attachment protein and 4 fusion proteins
40
What is the link between EBV latency and cancer?
- different latencys associated with different cancers
- II with gastrointestinal
- I with Burkitt's lymphoma
41
How does EBV-cancer change throughout the world?
different risk of EBV-associated cancer in different geographical regions perhaps due to different strains with different potentials to cause cancer
42
What types of Kaposi;s sarcoma are there?
- AIDS related
- lactogenic - immunosuppression
- sporadic
- endemic - non HIV re;ated
43
What cells are the initial major target for Dengue virus?
skin dendritic cells
enter the blood and reach their major targer: monocytes and macrophages
virus has also been isolated from lung, kidney, lymph nodes and more
44
What causes cell death in HBV?
- virus isnt directly cytopathic
- cell death caused by cellular recognition and killing of infected cells
45
HBV epidemiology
>50 primary liver cancer
different geographiocal regions have different cancer risks e.g. genotype C predominates in asia and has the highest risk of cancer
46
Where does measles virus infect?
- initially DCs and alveolar macrophages
- then reaches CD150+ lymphocytes
- can then also inter via nectin-4 into the basolateral surface of epithelial cells
47
What is special about the measles vaccine?
- CD45 upregulated in cancer
- delivery sysem for other ciruses such as chikungunya
48
What type of vaccine is the MMR vaccine?
live attenuated
49
How is HCV studied?
- replicons
- in vitro mammalian expression systems
- modified cell lines
50
What proteins are encoded in a HCV genome?
- E1 and E2
- RdRp
- NS2+3 proteases
- NS5A - innate immunity
51
what vaccines are available for HBV?
- inactivated vaccine made from the antigen particles of chronic carriers
- recombinant empty particles made in yeast cells (reduce issues with using plasma/blood)
- vaccines induce protective antiHBxAG in a 3 dose regime
- some such as older, obese males may need more dosese
52
What antivirals are used for HCV?
- PEG-IFN-a used to be used
- protease inhibitors that mimic NS3 cleavage sites and form tight long-lived complexes with NS3 and inhibit its action. used alongside PEG-IFN to reduece resistance. only works on genotype 1
53
How does RSV enter the cell?
- interacts with TLR4 or nucleolin
54
How does herpes simplex virus enter the host cell?
interaction of viral glycoproteins with host cell receptors
gB and gC bind cell surface proteoglycans
gD binds further herpes entry mediators to stabilise attachment
pH dependent fusion of the viral envelope with the plasma membrane
