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Molecular Microbiology > Influenza > Flashcards

Influenza Flashcards

1
Q

Influenza virus particle

A

-ssRNA
baltimore 5
segmented genome
spherical
lipid enveloped
family: orthomyxoviridae

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2
Q

Neuraminadase

A

enzyme on viral surface that cleaves sialic acid
helps movement of viral particle on surface of cell
helps virion release
tetramer

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3
Q

Haemagglutinin

A

Fusion glycoprotein
Homotrimer
Binds to sialic acid residues on cell surface receptors
crosslinked to matrix
HA1 and HA2
receptor binding pockets at top of trimer - 3 per subunit

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3
Q

HA2

A

grappling to endosome membrane
fuses viral membrane to endosomal membrane
allows virus to release contents
N-terminus refolds into stem of structure
The acidic environment of endosomes triggers a large-scale conformational change in the transmembrane subunit of HA (HA2) involving a loop (B loop)-to-helix transition, which releases the fusion peptide at the HA2 N terminus from an interior pocket within the HA trimer. Subsequent insertion of the fusion peptide into the endosomal membrane initiates fusion.

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4
Q

HA1

A

part of haemagglutinin that binds to sialic acid residues on receptors
non covalent disulphide linkage w HA2

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5
Q

NEP

A

Nuclear export protein
involved in early replication and switching off anti viral defenses
NEP involved in regulating the accumulation of viral genomic vRNA and antigenomic cRNA as well as viral mRNA synthesized by the viral RNA-dependent RNA polymerase.

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6
Q

Influenza genome

A

Negative sense segmented RNA genome
8 segments each coding 1 gene
associate w matrix protein shell
wrapped in nucleocapsidproteins for protection/packaging
each segment attached to RNAP heterotrimer

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7
Q

M2 ion channel

A

proton pump to acidify interior of viral particle when in endosome

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8
Q

influenza error prone replication

A

limits genome size
errors provide adaptability and evolves virus w mutations

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9
Q

cytokine storm

A

A severe immune reaction in which the body releases too many cytokines into the blood too quickly

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10
Q

where does influenza replicate?

A

nucleus

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11
Q

post translational modifications of HA

A

palmitoylation
trimerisation
glycosylation
stabilised by disulphide
trafficked to cell surface

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12
Q

when does cleavage of HA0 occur?

A

once the virus particle is outside of the cell to prevent early activation in host cell

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13
Q

Tryptase clara

A

type of host trypsin
cleaves HA0 into HA1 and HA2
arginine specific serine protease

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14
Q

influenza virus - cytokine - trypsin cycle

A

increase in proinflammatory cytokines leads to increase in trypsin concentration
more cleavage of HA0 = more infectious virus particles

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15
Q

sialic and galactose receptor linkages

A

alpha 2,6 in humans
alpha 2,3 in avian
mixture of both in swines

16
Q

Polyadenylation of influenza mRNA

A

PolyA tail encoded by UUUUU sequence in template
require for mRNA translation and stability

17
Q

Slippery sequences

A

not much hydrogen bonding between A and U (2 bonds)
polymerase stuttering - reads same base repeatedly = polyA tail

18
Q

Influenza RNA transcription

A

Produce viral mRNA
3 polymerase subunits -> PB1, PB2, PA
GTP base pairs with C at 3’ end of template
elongation

19
Q

mRNA cap

A

5’ methylguanylate cap
acts as primer for viral mRNA transcription

20
Q

where does influenza assembly occur?

A

cell surface

21
Q

palmitoylation

A

covalent attachment of palmitic acid to cysteine
important for HA/M1 interactions
involved in membrane fusion and curvature

22
Q

influenza replication

A

PB1 and PA involved only
1. NPs enter nucleus and melt panhandle once associated with viral RNA – induce switch from translation to replication
2. PA initiates primer independent positive strand synthesis (cRNA)
3. NPs bind and negative strand synthesis occurs

23
Q

PB1 subunit

A

endonuclease and catalytic polymerase

24
Q

PB2 subunit

A

recognition of cap structures

25
Q

PA subunit

A

involved in viral replication
RNAP subunit

26
Q

cap-snatching mechanism

A
  1. Cap bound by PB2
  2. Cleavage of mRNA cap after CA bases by PA
  3. U at 3’ template end base pairs with A in newly snatched cap primer
  4. 5’ and 3’ ends of RNA template loop and base pair with each other
27
Q

Panhandle

A

The 5′- and 3′- end sequences form a partial duplex (referred to as panhandle RNA), and this panhandle region functions as a promoter for viral transcription and replication by interacting with RNA-dependent RNA polymerase

28
Q

BANA113

A

NA inhibitor
Blocks active site of neuraminidase

29
Q

Human flu receptor

A

alpha 2,6 linkage sialic acid

30
Q

Avian flu receptor

A

alpha 2,3 linkage sialic acid

31
Q

Swine flu receptor

A

combination of sialic acid linkages

Molecular Microbiology (19 decks)

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