Influenza Flashcards
Influenza virus particle
-ssRNA
baltimore 5
segmented genome
spherical
lipid enveloped
family: orthomyxoviridae
Neuraminadase
enzyme on viral surface that cleaves sialic acid
helps movement of viral particle on surface of cell
helps virion release
tetramer
Haemagglutinin
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
HA2
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.
HA1
part of haemagglutinin that binds to sialic acid residues on receptors
non covalent disulphide linkage w HA2
NEP
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.
Influenza genome
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
M2 ion channel
proton pump to acidify interior of viral particle when in endosome
influenza error prone replication
limits genome size
errors provide adaptability and evolves virus w mutations
cytokine storm
A severe immune reaction in which the body releases too many cytokines into the blood too quickly
where does influenza replicate?
nucleus
post translational modifications of HA
palmitoylation
trimerisation
glycosylation
stabilised by disulphide
trafficked to cell surface
when does cleavage of HA0 occur?
once the virus particle is outside of the cell to prevent early activation in host cell
Tryptase clara
type of host trypsin
cleaves HA0 into HA1 and HA2
arginine specific serine protease
influenza virus - cytokine - trypsin cycle
increase in proinflammatory cytokines leads to increase in trypsin concentration
more cleavage of HA0 = more infectious virus particles
sialic and galactose receptor linkages
alpha 2,6 in humans
alpha 2,3 in avian
mixture of both in swines
Polyadenylation of influenza mRNA
PolyA tail encoded by UUUUU sequence in template
require for mRNA translation and stability
Slippery sequences
not much hydrogen bonding between A and U (2 bonds)
polymerase stuttering - reads same base repeatedly = polyA tail
Influenza RNA transcription
Produce viral mRNA
3 polymerase subunits -> PB1, PB2, PA
GTP base pairs with C at 3’ end of template
elongation
mRNA cap
5’ methylguanylate cap
acts as primer for viral mRNA transcription
where does influenza assembly occur?
cell surface
palmitoylation
covalent attachment of palmitic acid to cysteine
important for HA/M1 interactions
involved in membrane fusion and curvature
influenza replication
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
PB1 subunit
endonuclease and catalytic polymerase
PB2 subunit
recognition of cap structures
PA subunit
involved in viral replication
RNAP subunit
cap-snatching mechanism
- Cap bound by PB2
- Cleavage of mRNA cap after CA bases by PA
- U at 3’ template end base pairs with A in newly snatched cap primer
- 5’ and 3’ ends of RNA template loop and base pair with each other
Panhandle
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
BANA113
NA inhibitor
Blocks active site of neuraminidase
Human flu receptor
alpha 2,6 linkage sialic acid
Avian flu receptor
alpha 2,3 linkage sialic acid
Swine flu receptor
combination of sialic acid linkages
