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Amantadine Sensitive Virulent Qinghai H5N1 Bird Flu

Recombinomics Commentary

July 9, 2005

The H5N1 in Qinghai has acquired the PB2 mutation E627K, which could cause significant virulence issues, since the mutation increases virulence in lab mice and most mammals infected with H5N1 with the mutation have died.  Since all human flu isolates have this change, the acquistion of E627K by H5N1 makes it more human-like, which is cause for concern.

However, there was no mention of Amantadine resistance in either the Nature or Science paper.  There is no resistance markers in M2 in either parental strain (the chicken from Shantou and the peregrine falcon from Hong Kong).  Both of the parental strains have numerous migratory bird markers and there is little Amantadine resistance in migratory bird isolates.  The vast majority of isolates resistant to Amantadine are in Vietnam and Thailand (and probably Cambodia), so there is little reason to expect the Qinghai isolates to be resistant.  If they were, it is likely that the resistance would be mentioned in one or both papers, even if just as a footnote, since both were brief communications.

Amantadine is much cheaper than Tamiflu, although resistance could develop quickly.  All of the Vietnam and Thailand isolates have two resistant markers.  One is found only in those two countries.  The other marker is in a few H5N1 isolates in Indonesia, China, and Hong Kong.  Since most of the dead birds were bar headed geese, which migrate to Bangladesh and northern India, there is little reason to expect Amantadine resistance in the Qinhai isolates

The lethality of the Qinghai isolates in laboratory infected chickens and mice, coupled with the PB2 mutation in all Qinghai isolates, the H5N1 in Qinghai may pose a larger threat than H5N1 in Vietnam and southeast Asia.  It seems likely that the Qinghai H5N1 will spread far and wide as the birds migrate back to their wintering locations. 

Since there are no true H5N1 bird isolates with the PB2 mutation, the consequences on poultry and people are hard to predict.  However boxun reports indicate large numbers of people have already died and if true, the pandemic would already be at stage 6.  However, even if such reports are false or exaggerated, the introduction of PB2 H5N1 mutations in migratory birds has not been reported previously, and consequences could be global and severe.

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