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Swine Mutation PB2 V649I in Qinghai H5N1 Bird Flu

Recombinomics Commentary

July 10, 2005

The migratory bird H5N1 isolates at Qinghai Lake are accumulating mammalian polymorphisms, which mimics the pattern in Vietnam and Thailand.  As the H5N1 recombines and becomes more "human-like", it is more efficient at causing serious problems in humans.

As demonstrated in Figure S1 of the Science paper, the four Qinghai isolates BhGoose/QH/1/05, BhGoose/QH/2/05, BhGull/QH/1/05, and GbhGull/QH/1/05 all have another uncommon bird flu PB2 change, 
V649I, just downstream from E627K.  This PB2 change is also found in the 2004 Hong Kong peregrine falcon isolate, Pf/HK/D0028/04, which corresponds to G1971A in the PB2 gene. 

This polymorphism is relative rare in H5N1 isolates.  It is found in A/chicken/Guangdong/191/04, A/black headed gull/HK/12.1/2003, A/Ck/HK/WF157/2003, A/chicken/Hong Kong/31.4/02, A/chicken/Hong Kong/409.1/02, A/chicken/Hong Kong/96.1/02, A/duck/Guangdong/22/2002, A/duck/Fujian/17/2001.

Thus, although the first H5N1 with the sequence is in a duck from Fujian province, it is also found in an H5N1 isolate from a black headed gull, one of the species sampled at Qinghai Lake. 

The polymorphism can also be seen in additional isolates that are not as closely related.  These isolates are from Yunnan province (A/Ck/YN/115/2004, A/Ck/YN/374/2004, A/Dk/YN/6255/2003, A/Dk/YN/6445/2003), where Qinghai birds migrate, and Shantou province (A/Ph/ST/44/2004), where the parent, A/Ck/ST/4231/03, for the Qinghai HA, NA, and NP genes was isolated.

Thus, the distribution pattern of this polymorphism is consistent with the movement of this polymorphism by migratory birds.  However, prior to the appearance in H5N1 isolates at GenBank, the polymorphism was found in mammalian isolate in H1N1 and H1N2 swine in Europe and H3N2 swine in Hong Kong, such as A/swine/Ille et Vilaine/1455/99, A/swine/Italy/2064/99, A/swine/Hong Kong/1197/02, respectively. The mutation is found as early as 1981 in swine, A/Swine/Germany/2/81.

Publication of the full sequences will allow for more extensive analysis, but recombination is alive and well and being used by Qinghai isolates to gather up mammalian polymorphisms such as PB2 E627K and V649I , just as H5N1 isolates in Vietnam and Thailand did in 2004.

The boxun reports on human victims of H5N1 in Qinghai are gaining credibility.

The story is in the sequence and H5N1 does not read press releases.

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