Transcript What makes H5N1 Avian influenza Avian?

What makes H5N1 Avian influenza “Avian”?
(why not “H5N1 Tiger influenza”?)
Finding mutations that limit the
transmission of avian influenza to other
species…especially humans
(But also tigers).
Tad Davenport
CSE140 March 18,2013
H5N1 Influenza Background
Hemagglutinin (HA)
The “H” in H5
Helps the virus enter host cells
Neuraminidase (NA)
The “N” in N1
Helps the virus “escape” host cells
From: gridpp.ac.uk
H5N1 Avian Influenza: “Bird flu”
Extremely prevalent in birds
Seasonal Influenza: H1N1 and H3N2
3,000 – 50,000 deaths/year (US)
But it is rarely transmitted to humans
http://www.cdc.gov/flu/about/disease/us_flu-related_deaths.htm
Pandemic Influenza: e.g. The “Spanish Flu”
10-20% of those infected died
50-100 Million deaths
?
http://en.wikipedia.org/wiki/1918_flu_pandemic
However, upon transmission it has a
High mortality rate (~60%)
http://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N1
Research Question:
Why is bird flu poorly transmitted to humans?
Are H5N1 viruses that infect humans (and other mammals) different from
H5N1 viruses that infect birds?
If so: where do these differences occur?
Approach:
Focus on Hemagglutinin (HA) sequences (because the virus uses this protein to enter host cells)
Find the most common HA sequence for each species, a.k.a. the “consensus” sequence
Compare the consensus sequences for all available species, find the amino acid changes
Program Output: Mutations At HA Receptor Binding Site
Changes in Human H5N1 relative to
Avian H5N1 isolates:
[('N', 170, 'S'), ('A', 171, 'T')]
Amino Acid Number
Imai, M. Nature 2012
Interpretation and Conclusions:
These naturally-occurring mutations occur at a site (N158D) that has been
previously shown to be important for adaptation of H5N1 to be transmissible
between ferrets in laboratory experiments. (Imai, M. et al. Nature 2012).
Because these mutations occur in multiple species, this suggests that they
have been selected for in multiple, independent transmission events
They occur at the receptor binding
site!
All of these suggest that they are
functionally important mutations
that may limit transmission
between birds and mammals.
http://www.virology.ws/2012/06/21/influenza-h5n1-virus-versus-ferrets-round-two/