Dr. Mubareka's session

Question 1

What does IRES stands for?

Answer 1

internal ribosomal entry site

Question 2

function of IRES

Answer 2

i) help end-independent ribosomal recruitment
ii) help new interactions with eIFs

Question 3

where is IRES found?

Answer 3

polio
–> picovirus

Question 4

How is host cell translation shut off with IRES?

Answer 4

poliovirus protease 2A cleave eIF4G

Question 5

Which viruses are enveloped?

Answer 5

Flavivirus, Coronavirus, Bunyavirales

Question 6

Which viruses lack an envelope?

Answer 6

piconavirus, orthomyxovirus (influenza), reovirus

Question 7

What is the source of vaccine derived poliovirus?

Answer 7

from oral polio vaccine (when unvaccinated ppl contact with oral vaccinated ones)

Question 8

What sites are known for evolution of vaccine derived poliovirus?

Answer 8

i) revert sites for low neurovirulence
ii) revert site of reduced replicative fitness

Question 9

How is piconavirus transmitted?

Answer 9

fecal-oral, respiratory

Question 10

Why is cancer cells more susceptible to reovirus infection?

Answer 10

Ras expression
–> inhibit dsRNA dependent (PKR)
–> reovirus get endocytosed + replicate inside cells

Question 11

viruses with non-segmented genome

Answer 11

Mononegavirales, Coronavirus, Flavivirus, picovivirus

Question 12

negative sense viruses

Answer 12

Mononegavirales, Orthomyxovirus, Bunyavirales

Question 13

Function of PKR in viral replication

Answer 13

after activated by dsRNA during viral replication
–> stops viral dsRNA synthesis (reovirus)

Question 14

How does oncolytic virotherapy work for reovirus?

Answer 14

i) release of cytokines
ii) activate antigen presenting cells
iii) killing of tumor cells thru NK cells and CD8 T cell

Question 15

Viruses with segmented genome

Answer 15

reovirus, bunyavirales, orthomyxovirus

Question 16

positive sense viruses

Answer 16

piconavirus, flavivirus, coronavirus

Question 17

viruses belong to neither + and - sense

Answer 17

reovirus

Question 18

Feature special to reovirus

Answer 18

RNA always attached to inner capsid

Question 19

forms of reovirus

Answer 19

i) virion
ii) ISVP
iii) core particle

Question 20

which forms of reovirus is infectious?

Answer 20

virion, ISVP

Question 21

where is N protein found?

Answer 21

Bunyavirales

Question 22

Roles of N protein

Answer 22

i) initiates transcription
ii) RNA chaperone
iii) primed mRNA synthesis from genome
iv) form vRNA from cRNA
v) transcription templates as ribonucleoproteins

Question 23

How does N protein initiates transcription?

Answer 23

i) bind to panhandle on vRNA
ii) unwinds panhandle + allow RdRp to interact at 3’ term

Question 24

what are some injuries linked to hantavirus?

Answer 24

acute lung and kidney injury

Question 25

What contributes to lung and kidney injuries in hantaviral infection?

Answer 25

i) increased permeability ii) thrombocytopenia (less platelets) ii) complement activation

Question 26

How is permeability increased in hantavirus infection?

Answer 26

i) VEGFA upregulated --> downregulates VE cadherin ii) secretion of bradykinin

Question 27

How does orthomyxovirus initiates transcription?

Answer 27

cap snatching

Question 28

Where does cap snatching occur?

Answer 28

nucleus for influenza

Question 29

function of PA subunit in transcription initiation of influenza

Answer 29

cleave 5' cap in host transcript

Question 30

describe steps in cap snatching

Answer 30

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

Question 31

What can enter PB1 in RdRp of influenza?

Answer 31

i) NTPs ii) vRNA

Question 32

Proteins and subunits needed for cap snatching

Answer 32

i) RdRp - PB2 (align the two pieces) - PA (cleave 5' cap from trascript) - PB1

Question 33

What holds vRNA during transcription initiation?

Answer 33

binding pocket in PB1 holds 5' end of vRNA

Question 34

What contributes to the variety in influenza?

Answer 34

i) antigenic drift ii) antigenic shift iii) recombination

Question 35

How does antigenic shift contirbute to influenza evolution?

Answer 35

allow different strains of influenza to mix tgt --> change surface antigen --> change genome material

Question 36

How does recombination help with influenza evolution?

Answer 36

have segments with genetic material from more than one source --> increase cleavability of HA

Question 37

How does antigenic drift contribute to influenza evolution?

Answer 37

minor changes in virus --> not recognzied by previous antibodies maybe

Question 38

Thru what process does Ebola get into cells?

Answer 38

macropinocytosis

Question 39

What factors on ebola interact with cell surface?

Answer 39

glycoprotein 1, 2 (forming trimer)

Question 40

What does Ebola bind on cells for entry?

Answer 40

i) attachment factors ( C type lectins) ii) receptors (TIM-1)

Question 41

what helps with macropinocytosis of ebola?

Answer 41

TAM family members (tyrosin kinase receptor)

Question 42

Describe steps in ebola entry

Answer 42

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

Question 43

What happens after ebola genome enters cytosol?

Answer 43

i) replicated in cytosol ii) transcribed into mRNA + translated --> GP translated in ER iii) virion assembly

Question 44

Where does ebola infection usuallly occur?

Answer 44

dendritic cells, monocytes, macrophages --> reduced innate immune response broad cell tropism

Question 45

Why is bat such a great viral reservoir?

Answer 45

i) intruded by humans ii) huge colony + dense iii) hibernation iv) flight v) long life span, synchronized parturition

Question 46

How does flight help bat as a reservoir?

Answer 46

allow them to migrate all over and get different viruses --> their immunity allows them to tolerate virus

Question 47

How ds hibernation help bat as a viral reservoir?

Answer 47

lower their body temp --> allow virus to persist inside them

Question 48

How does human enroachment help bat as a viral reservoir?

Answer 48

mix with other viruses present in domestic animals/human --> acquire receptors within human

Question 49

Strategies used by coronavirus for making subgenomic RNA transcript

Answer 49

template switching

Question 50

How does template swithcing works

Answer 50

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

Question 51

When is S1/S2 junction cleaved in covid?

Answer 51

i) trafficking by furin like enzyme ii) serine protease (TMPRSS2) during attachment iii) cathepsin in late endosome

Question 52

when is S2' cleaved by cathepsin

Answer 52

enter thru ACE2

Question 53

when is S2' cleaved by TMPRSS2

Answer 53

bind to nearby receptor that has TMPRSS2 close to it

Question 54

What cleaves S protein and when in covid?

Answer 54

by furin in golgi apparatus --> S1 (receptor bind) + S2 (mediate fusion)

Question 55

Common vectors for flavivirus

Answer 55

i) A. aegyti ii) A. albopictus

Question 56

What is the feature of infectious virions in flavivirus?

Answer 56

those whose prM is completely cleaved

Question 57

what helps partially mature virions for flavivirus to enter cells?

Answer 57

furin protease

Question 58

what happens when more partially mature virions enter cells

Answer 58

increase infectivity of immature dengue virus --> higher conc of antibody

Question 59

In what virus is antibody-dependent enhancement observed?

Answer 59

flavivirus

Question 60

What happens in antibody dependent enhancement?

Answer 60

i) PRR signalling decrease --> less interferon production --> more virions produced

Question 61

Order the geographic distribution of Virus (From most limited to broadest)

Answer 61

i) Flavivirus (limited to tropics) ii) Mononegavirales iii) Bunyavirales (restriction based on reservoir) iv) Coronavirus = orthomyxovirus (some geographic restriction) vi) piconavirus = reovirus (Global)