influenza the virus life cycle lectures 1 and 2 Flashcards
how is H5N1 influenza virus spread
by bird migration
what does it mean by negative sense strand
is complementary to the positive strand and doesn’t code for proteins they have no useful ORFs
how can negative strands become useful
must be transcribed to positive sense copies
what are the genome segments assembled into
ribonucleoproteins or RNPs
what are the 3 parts to the segment
lopped end, central filament region, RNA polymerase end.
what hapeens to the 2 ends in the RNP
they are forced together and bend into a hairpin shape.
how are the ends held together
watson-crick interactions or ends can interact with complex of 3 protiens called the RNA-dependent RNA polymerase .
What does the nucleoprotein NP do
forms a chain to entirely cover the RNA
what does chain formation depend on
the NP-NP interaction through the tail loop and the RNA binding in a groove on the NP surface.
which proteins are needed for RdRp
PB1, PB2, PA
what is the matrix protein needed foR
structure, shape M2 protein, ion channel.
what is NS1 needed fot
IFN antagonist, RNP epxort
what is NS2 needed for
RNP export
how is sialic acid related to galactose
has either 2-3 or 2-6 alpha linkage
what cell type linkage does human flu moslty infect
2-6
whta is HA initially synthesised to
HA0
what is HA0 cleaved to
HA1 AND HA2
what is cleavage done by
proteases e.g furin
what do HA1 and 2 form
1 forms the globular head and 2 forms the long stalk via a 6 helix bundle. receptor binding site is in HA1 domain.
how does the fusion peptide become active
it is re positioned from in HA0 to the amino terminus. done when HA 1 and 2 are cleaved.
what triggers conformational chnage exposing fusion peptide
ph5 this aligns HA2 and peptide goes upwards and inserts into endosome membrane
what are the 2 critical functions of HA
1-virus attachment
2-virus entry
what is M2
a viroporin allows release of RNP
what other factors does RNP release need
EPS8, TNP01, HDAC6
what doe individual NPmonomers have
2 import signals
what is exposed in formed RNPs
NLS1
what does NLS1 do and lead to
recruits importin alpha then beta importin is recruited. RNP/importin complex binds pore and the RNPs enter the nucleus
what does trnascription result in
generation of one RNA trnascript per segment
what is the 1st stage of transcription
RdRp PB2 binds to mRNA and PA steals the 5 cap
what is the 2nd stage
RdRp and capped oligonucleotide bind to negative strand RNA genome
what is the 3rd stage
RdRp PB1 uses capped RNA to begin transcription
what is the 4th stage
RdRp moves along the template, PB1 geberates RNA trnacript with 5 cap and 3 poly A tail.
what is the fate of Influenza mRNA and their products
HA, NA, M2 NS1 stay in cytoplasm for assembly.
NP, PB1, PB2, PA, M imported to nucleus to make more RNPs
what is the 1st stage of replication
RdRp binds 3 end of RNA segment no primer
2nd stage of replication
RdRp travels to 5 end make complementary copy.
3rd stage of replication
NP wraps RNA as it’s made
4th stage of replication
cycles of replication allow amplification of genomes.
what does NS2 do
binds M forms outer layer on RNP has an export signal that masks all other signals.
what does CRM1 do
allows NS2 to engage host cell machinery for export. It binds to Ran-GTP and exits NPC.
what needs to reach the apical surface of the plasma membrane
all 8 segments and HA, NA, M1 and M2
how ae HA, NA and M2 trafficked
via secretory pathway
how are the RNPs abd M1 trafficked
on recycling endosomes. RNP interacts with Rab11.
what does M1 associate with
cytoplasmic tails of HA, NA, and M2
