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trevor hedges

on 11 February 2010

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Transcript of evolution

Molecular Evolution of The Influenza virus By Trevor Hedges 10 influenza pandemics over the past two centuries
50 million casualities from 1918 pandemic alone
Rapid evolution of viral genome allows it to evade immune system attacks
Current Influnza A strain is assigned phase 6 pandemic level
Structure and Function An integral membrane protein acts as main surface antigen
Binds to host cell receptors
First part of strain named after serotype of HA Form a polymerase complex for RNA synthesis Second surface antigen
responsible for cleavage of terminal amino acid on glycolipid
Free virus from host cell
Second part of strain named after serotype of NA Hemagglutinin Neuraminidase PANDEMICS! The evolving virus 3 mechanisms by which the genome evolves Mutations Genome reassortment Selective sweeps RNA polymerase has low copy fidelity
1 error every 10000 bases
The infection of two different viruses in one host can result in genetic transfer Positively selected mutations pull through neutral mutations Mutations must allow the virus

to overcome two barriers 1. Overcome the host to human transmission barrier

2. Continued replication in human host Mutations in surface antigens responsible for host cell recognition Hemagglutinin Neuraminidase mutation in proteins that increase virulence Nucleoprotein Polymerase PB1-F2 Hemagglutinin 1918 Spanish Flu Antigenic Shift lead to the introduction of a new hemagglutinin serotype into human population- H1
No previous infections meant no antibodies, so everyone was at risk

Caused elevated immune response leading ot cytokine storm NA HA PA PB1 PB2 M2 M1 NP How do they occur? H1N1 influenza A Quadruple reassortment virus orignating in swine Common method of reassortment in Swine strains Pigs contain cell receptors for both avian and human virus which can result in novel reassortments Concerns Two point mutations in the PB1-F2 gene could significantly increase virulence Lacks PB1-F2 virulence associated gene Reassortment with highly virulent H5N1 or another PB1-F2 containing virus could result in high pathogenicity Has overcome both transmission barriers
Overview The structure and Function of influenza virus

Evolution of a pandemic strain

The spanish flu

2009 H1N1 outbreak

Increased virulence from group of polymerase proteins PB2 in this strain found to be efficient at 33°C and 37°C
Allowed growth in upper and lower respiratory tract which increased cases of pneumonia Conclusion The newly reassorted strain of H1N1 has the ability to cross the species barrier and transmit from human to human
It has yet to gain high pathogenicity
There are still concerns over the ability of the strain to mutate into more virulent form through point mutations and gene reassortments 2009 Swine flu Capable of interspecies transfer and human to human transmission Considered half an antigenic shift- still H1 serotype 20% divergence from H1 40% divergence from H2 Lack of antibodies towards virus due to large divergence three H1N1 pandemics in1918, 1957, 1977 but only show effective antibodies in people born before 1918 Introduction of drug resistance QUESTIONS ?
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