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 H5N1 Avian Influenza: “Bird flu” Extremely prevalent in birds But it is rarely transmitted to humans However, upon transmission it has a High mortality rate (~60%) http://en.wikipedia.org/wiki/Influenza_A_virus_subtype_H5N1 From: gridpp.ac.uk ? Seasonal Influenza: H1N1 and H3N2 3,000 – 50,000 deaths/year (US) 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

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')] Imai, M. Nature 2012 Amino Acid Number

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/