Dr. Mubareka's session Flashcards
What does IRES stands for?
internal ribosomal entry site
function of IRES
i) help end-independent ribosomal recruitment
ii) help new interactions with eIFs
where is IRES found?
polio
–> picovirus
How is host cell translation shut off with IRES?
poliovirus protease 2A cleave eIF4G
Which viruses are enveloped?
Flavivirus, Coronavirus, Bunyavirales
Which viruses lack an envelope?
piconavirus, orthomyxovirus (influenza), reovirus
What is the source of vaccine derived poliovirus?
from oral polio vaccine (when unvaccinated ppl contact with oral vaccinated ones)
What sites are known for evolution of vaccine derived poliovirus?
i) revert sites for low neurovirulence
ii) revert site of reduced replicative fitness
How is piconavirus transmitted?
fecal-oral, respiratory
Why is cancer cells more susceptible to reovirus infection?
Ras expression
–> inhibit dsRNA dependent (PKR)
–> reovirus get endocytosed + replicate inside cells
viruses with non-segmented genome
Mononegavirales, Coronavirus, Flavivirus, picovivirus
negative sense viruses
Mononegavirales, Orthomyxovirus, Bunyavirales
Function of PKR in viral replication
after activated by dsRNA during viral replication
–> stops viral dsRNA synthesis (reovirus)
How does oncolytic virotherapy work for reovirus?
i) release of cytokines
ii) activate antigen presenting cells
iii) killing of tumor cells thru NK cells and CD8 T cell
Viruses with segmented genome
reovirus, bunyavirales, orthomyxovirus
positive sense viruses
piconavirus, flavivirus, coronavirus
viruses belong to neither + and - sense
reovirus
Feature special to reovirus
RNA always attached to inner capsid
forms of reovirus
i) virion
ii) ISVP
iii) core particle
which forms of reovirus is infectious?
virion, ISVP
where is N protein found?
Bunyavirales
Roles of N protein
i) initiates transcription
ii) RNA chaperone
iii) primed mRNA synthesis from genome
iv) form vRNA from cRNA
v) transcription templates as ribonucleoproteins
How does N protein initiates transcription?
i) bind to panhandle on vRNA
ii) unwinds panhandle + allow RdRp to interact at 3’ term
what are some injuries linked to hantavirus?
acute lung and kidney injury
What contributes to lung and kidney injuries in hantaviral infection?
i) increased permeability
ii) thrombocytopenia (less platelets)
ii) complement activation
How is permeability increased in hantavirus infection?
i) VEGFA upregulated –> downregulates VE cadherin
ii) secretion of bradykinin
How does orthomyxovirus initiates transcription?
cap snatching
Where does cap snatching occur?
nucleus for influenza
function of PA subunit in transcription initiation of influenza
cleave 5’ cap in host transcript
describe steps in cap snatching
i) viral RNP bind to CTD of Pol II
ii) PB2 capture a capped transcript, then cleaved by PA subunit
iii) PB2 swivels to align 3’ of cleaved gragment to template inPB1 subunit
What can enter PB1 in RdRp of influenza?
i) NTPs
ii) vRNA
Proteins and subunits needed for cap snatching
i) RdRp
- PB2 (align the two pieces)
- PA (cleave 5’ cap from trascript)
- PB1
What holds vRNA during transcription initiation?
binding pocket in PB1 holds 5’ end of vRNA
What contributes to the variety in influenza?
i) antigenic drift
ii) antigenic shift
iii) recombination
How does antigenic shift contirbute to influenza evolution?
allow different strains of influenza to mix tgt
–> change surface antigen
–> change genome material
How does recombination help with influenza evolution?
have segments with genetic material from more than one source
–> increase cleavability of HA
How does antigenic drift contribute to influenza evolution?
minor changes in virus
–> not recognzied by previous antibodies maybe
Thru what process does Ebola get into cells?
macropinocytosis
What factors on ebola interact with cell surface?
glycoprotein 1, 2
(forming trimer)
What does Ebola bind on cells for entry?
i) attachment factors ( C type lectins)
ii) receptors (TIM-1)
what helps with macropinocytosis of ebola?
TAM family members (tyrosin kinase receptor)
Describe steps in ebola entry
i) GP on ebola interact with C type lectin, receptors like TIM-1
ii) virions get in by macropinocytosis
iii) GP cleaved by cathespin B, L –> expose receptor binding site
iv) acidification in endosome
–> GP1 interact with NPC1
–> enter cytosol
What happens after ebola genome enters cytosol?
i) replicated in cytosol
ii) transcribed into mRNA + translated
–> GP translated in ER
iii) virion assembly
Where does ebola infection usuallly occur?
dendritic cells, monocytes, macrophages
–> reduced innate immune response
broad cell tropism
Why is bat such a great viral reservoir?
i) intruded by humans
ii) huge colony + dense
iii) hibernation
iv) flight
v) long life span, synchronized parturition
How does flight help bat as a reservoir?
allow them to migrate all over and get different viruses
–> their immunity allows them to tolerate virus
How ds hibernation help bat as a viral reservoir?
lower their body temp
–> allow virus to persist inside them
How does human enroachment help bat as a viral reservoir?
mix with other viruses present in domestic animals/human
–> acquire receptors within human
Strategies used by coronavirus for making subgenomic RNA transcript
template switching
How does template swithcing works
once form TRS-B on 5’ end
–> can skip over some parts of genome
–> TRS-B pair with TRS-L on 3’ end and complete transcription
When is S1/S2 junction cleaved in covid?
i) trafficking by furin like enzyme
ii) serine protease (TMPRSS2) during attachment
iii) cathepsin in late endosome
when is S2’ cleaved by cathepsin
enter thru ACE2
when is S2’ cleaved by TMPRSS2
bind to nearby receptor that has TMPRSS2 close to it
What cleaves S protein and when in covid?
by furin in golgi apparatus
–> S1 (receptor bind) + S2 (mediate fusion)
Common vectors for flavivirus
i) A. aegyti
ii) A. albopictus
What is the feature of infectious virions in flavivirus?
those whose prM is completely cleaved
what helps partially mature virions for flavivirus to enter cells?
furin protease
what happens when more partially mature virions enter cells
increase infectivity of immature dengue virus
–> higher conc of antibody
In what virus is antibody-dependent enhancement observed?
flavivirus
What happens in antibody dependent enhancement?
i) PRR signalling decrease
–> less interferon production
–> more virions produced
Order the geographic distribution of Virus (From most limited to broadest)
i) Flavivirus (limited to tropics)
ii) Mononegavirales
iii) Bunyavirales (restriction based on reservoir)
iv) Coronavirus = orthomyxovirus (some geographic restriction)
vi) piconavirus = reovirus
(Global)
