Last week the NSABB announced that the two controversial papers discussing mammalian transmissible H5N1 authored by Yoshihiro Kawaoka of University of Wisconsin Madison and Ron Fouchier of Erasmus Medical Center. The bare minimal story in his paper was revealed by Ron back in September at a conference in Malta and again in February at a meeting of the ASM. However, nothing had been revealed about Kawaoka's work until yesterday.
Long story short, I am even more confused as to why this work was blacked out in the first place and a little underwhelmed by the results. I guess that is why the board voted unanimously to allow his work to be published. Basically, Kawaoka took the HA (the protein responsible binding and entering cells; also responsible for species specificity) from H5N1 made a bunch of variations with a bunch of mutations and checked each one for human specificity. He then took a human specific version and plugged it into a virus with other genes from the 2009 pandemic virus.
To recap, this is a virus with 7 fully human flu genes, plus an "avian" gene that has been heavily modified to look human. When they analyzed the HA gene they found 4 mutations. N158, Q226L, N224K, and T318I. If you think of a protein as a chain, Q226L means the 226th link in the chain was changed from a Q, glutamine, to L, leucine. Three of these mutations are fairly well understood. N158 sits right near a glycosylation site. Glycosylation sites are where sugar molecules are stuck to the protein and can be thought of kind of like a costume for the virus. Changing the pattern of sugar on the proteins can alter where the virus can bind and how the immune system "sees" and responds to the virus. The loss of glycosylation right near this mutation has been known to cause a preference switch to human cells. The mutations at 224 and 226 sit directly in the area that actually binds to the cell surface, the receptor binding site, or RBS. Making these mutations physically changes the shape of the RBS so different cellular parts fit it. Its like those kid toys with the shaped blocks that fit in different holes. With one set of mutations you have a triangle hole that fits the triangle pegs on a birds cell. Change those to another set and you get a circular hole that won't fit bird pegs anymore, but will fit the human circular pegs.** The last mutation, T318I, I have no idea about. It will be interesting to see the follow up experiments they do with that mutation.
The virus Kawaoka's team made was able to infect and transmit by respiratory droplets. Basically when a ferret sneezes it looks like this:
So we have a highly unnatural, reassorted virus that causes limited disease, but does transmit through the air. What the hell was the last 4 months about?
**slightly more complicated than triangles and circles.