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There are 2 big questions regarding influenza and species jumps. 1) What changes does the virus need to adapt to a new species, and 2) what changes does the virus need to be easily transmitted within that species? A paper in press by Gambaryan et al. (found in the journal Virology, here) sheds some light onto the first question, at least regarding H5N1. And the answer is: not many changes are necessary at all--as little as one amino acid change can alter the binding specificity.
The fact that a single amino acid substitution in the receptor binding area of the H5 HA of two human isolates, A/Hong Kong/212/2003 and A/Hong Kong/213/2003, resulted in marked affinity to a receptor optimal for typical human viruses underscores the necessity and significance of further comprehensive surveillance for the affinity of H5N1 viruses to different receptors for better understanding of their pandemic potential.As always, EffectMeasure is one step ahead of me, and has a more thorough discussion of the results here.