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Commentary
Wild Birds Have
Most Kawaoka H5N1 Transmission Changes
Recombinomics
Commentary 10:30
April 17, 2012
However, Kawaoka noticed that one of the ferrets he infected had especially high levels of virus in its nose. These viruses had picked up a third HA mutation — N158D — and could now spread between neighbouring ferrets. Kawaoka found that two of six healthy animals picked up infections from neighbours they had no contact with. Along the way, the virus acquired a fourth mutation — T318I.
Three of these mutations are new, at least in public databases. N158D is the only one of the four mutations that has been documented in wild birds.
The above comments are from a Nature description of the transmission changes found in the Yoshi Kawaoka paper, which has been unanimously recommended for publication (by the same NSABB members who previously unanimously recommended censorship of the paper).
The Kawaoak paper, however is far more useful when analyzed with the CDC paper that was published in Virology, prior to the NSABB discussions, as well as the Ron Fouchier paper accepted by Science, which is still under discussion, even though a majority of NSABB voted to publish the paper in full.
The CDC achieved ferret to ferret airborne transmission without passage in ferrets, in contrast to the Kawaoka method described above, or the Fouchier paper, which began with the two HA changes that have been widely discussed, Q226L and G228S, (which were also used in the CDC paper). These two changes were present in sequences from the 1957 and 1968 pandemics (which involved H2 and H3), but have never been reported in natural H5 isolates. They are the changes cited by WHO when assurances are given regarding the failure of a human isolate to acquire the “mammalian” receptor binding domain (Q226L and G228S). Thus, the three papers provided experimental validation for concerns regarding these two changes, since all three papers used H5 with Q226L, and two of the three also started with G228S.
However, the Kawaoka paper demonstrated the ability of N224K to substitute for G228S, and although the Nature summary states that only N158D has been found in the wild (see above quote), the Nature summary is false. N224K has been found in H5N1 in Egypt (A/duck/Egypt/10185SS/2010) and Vietnam (A/Muscovy duck/Vietnam/NCVD-11/2007), while T318I has been found in China (A/mallard/Xuyi/10/2005, A/spotbill duck/Xuyi/18/2005, A/duck/Guangxi/53/2002).
Thus, the Kawaoka paper highlights H5N1 ferret transmission via four HA changes, which includes three that are already circulating in nature, instead of just one (N158D) which is widespread in wild birds (clade 2.2 and clade 2.3). The Kawaoaka paper, as well as the Fouchier paper, started with H5 which glycosylated position 158, which was eliminated via ferret passage in the Kawaoka paper, which almost certainly happened in the censored Fouchier paper.
The natural circulation of three of the four changes used in the Kawaoka paper in wild birds, as well as the accumulation of two of the four in current H5N1 in Egypt, highlights the need for a critical review of the expertise on the NSABB board, and the dangers of publication of important scientific observations via press release.
The current NSABB board continues to be hazardous to the world’s health, exceeding the risk posed by putative bioterrorists.
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