I've just come back from the first morning of the Royal Society meeting on pathogenic H5N1 avian influenza. Some excellent overviews of the virus, plus presentations from the two principle investigators on the recent ferret transmission studies, Yoshihiro Kawaoka and Ron Fouchier.
Professor Kawaoka was able to talk in full about his findings on the role of hemagglutinin in mammalian transmission of H5 viruses.
They created a library of H5 mutant viruses and then screened for their ability to bind to the specific receptor (α2,6 - sialic acid) found in the upper respiratory tract of mammals. To perform the ferret transmission studies they then created a re-assortment of the recent H1N1 2009 pandemic flu such that it carried a selected mutant H5 (instead of H1).
They passaged this virus in ferrets and eventually observed reasonable aerosol transmission. 4 mutations were mapped to the HA gene; N224K, N226L, N158D and T318I. The 224 and 226 mutations altered receptor binding. However, these changes also destabilized the fusion activity of HA, the T318I mutation compensated for this deficiency. The N128D mutation removes a glycosylation site and is thought to contribute to both receptor binding and fusion stability.
Critically, in these experiments the reassorted H5N1 virus did not transmit as readily as H1N1 2009 and did not kill any ferrets, or make them particularly ill for that matter.
Unfortunately Ron Fouchier remains gagged by the Dutch government. He essentially gave the same presentation discussed by +Vincent Racaniello
at virology blog. He observed H5N1 avian influenza adapted to aerosol transmission between ferrets, but it was only lethal when large amounts were artificially introduced into the nose or throat of the animals. He could not state the mutations. Although he did reveal that they have found critical mutations in genes other than HA.
It's great that the data is seeing the light of day. Just a shame I'm missing the rest of the discussion on the politics and ethics of such research, alas the electron microscope is calling me.........