Infleunza Part2 Wk4 Flashcards
Transcription of virus mRNAs use fragment of cellular mRNA
Cellular mRNA transcription
- rapid addition of 5’ universal gap
Influenza virus polymerase complex is bound to every genome segment
PB2 protein binds the 5’-cap of cellular mRNA
PB1 & PA proteins work in concert as an endonuclease
= cleaves capped RNA (~10-15nt from the cap)
cap snatching
Influenza virus polymerase complex
PB1 binds to both
-mRNA fragment with 5’-cap
-3’-end of genomic vRNA
=polymerase function
PB1 protein transcribes (+)ssRNA using
-mRNA fragments (with 5’-cap) as a primer
-genomic vRNA as a template
On reaching 5’end of vRNA template
(=3’end of the new (+)RNA)
The PB1 polymerase produces a polyA tail by reiterative stuttering
=repeated transcription on a short polyUTP sequence in the vRNA
Results of transcription = capped, polyadenylated chimeric mRNAs
5’-region is a fragment of cellular mRNA
Remainder is (+)ssRNA copy of (-)vRNA
5’-cap & polyA tail promote
-exit from cell nucleus
-translation by cell ribosomes
Influenza A virus replication cycle - genome replication
Is also RNA transcription but doesnt involve cap-snatching
Free rNTPs bind to the 3’-end of each of the cRNAs
PB1 polymerase protein forms a phosphodiester bond
PB1 transcribes (-)ssRNA from this dinucleotide primer
No 5’-cap is added - this is cRNA, not mRNA
(+) sense cRNA intermediates associated with with NP and polymerase
A virus replication cycle - assembly & genome packaging
vRNAs & cRNAs associate with PB1, PB2, PA & NP in nucleus
Only vRNPs exit the nucleus - mediated through binding with M1 & NS2 proteins
M1 interacts with structual virus proteins at the plasma membrane
Plasma membrane & matrix layer wrap around vRNPs
Random / selective incorporation model
Influenza A replication cycle - budding release
Exit by budding - gains envelops
Neuraminidase cleaves bonds
Also prevents virion aggregation
HA on new virions binds neuraminidase acids
On other virions
Neuraminidase protein is a targets for antiviral drugs
Influenza virus pathogenesis
Acut, contagious infections of upper respiratory tract
-virus shed into respiratory lumen
-no systemic spread
-immune pathology
-self-limiting (strong immunity)
Fatalities rare
-elderly, young, immune-compromised
-viral / bacterial pneumonia
Influenza virus epidemics and pandemics
Seasonal recurrence of flu epidemics
-pandemic outbreaks also recorded through history
Influenza A virus genetic diversity, change + exchange
Advantageous mutations in human influenza/avian or swine influenza virus strains = new combinations of genome segments between human, avian & swine influenza virus strains.
