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North Vietnam H5N1 Cleavage Site Matches Central Guangdong

Recombinomics Commentary
May 25, 2005

>> A/Duck/Guangdong/173/04 (H5N1) (Dk/GD/173/04 in brief, Central Guangdong), A/Chicken/Guangdong/174/04 (H5N1) (Ck/GD/174/04 in brief,Western Guangdong),A/Chicken/Guangdong/178/04 (H5N1) (Ck/GD/178/04 in brief, Eastern Guangdong), and A/Chicken/Guangdong/191/04 (H5N1)(Ck/GD/191/04 in brief, Northern Guangdong).

The alignment of the derived amino acid sequences of these four AIVs shows that Ck/GD/174/04 has the same motif of basic amino acids (RRRKKR) as most of other public H5N1 2003-04 outbreak strains between the two domains of HA(HA1 and HA2) [12]. However, Ck/Gd/178/04 and Ck/GD/191/04 have a deletion of nucleotides in this bridge, which results in a loss of an amino acid K at the fifth position within the motif RRRKKR, as in A/duck/China/E319.2/03. In contrast, Dk/Gd/173/04 lost the R residue at the first position within this motif, and its motif is RRKKR. <<

The above comments are from a recently published paper, "Genetic characterization of H5N1 avian influenza viruses isolated in southern China during the 2003-04 avian influenza outbreaks" which describes four H5N1  isolates from Guangdong. 

As noted above, the four isolates contain three different sequences in their HA cleavage site.  The isolate from Western Guangdong has a cleavage site common to most of the H5N1 isolates, including the 2004 isolates from Vietnam and Thailand. 

The isolates from Eastern and Northern Guangdong have a cleavage site that has lost a lysine residue.  The motif matches the sequence from the isolate from a duck smuggle from Shanghai unto Quemoy Island in Taiwan.  This motif has also been detected in 2004 isolates from eastern provinces in China as well as South Korea.

The duck from Central Guangdong has lost an arginine in cleavage site.  This motif is found in the 2005 isolates in northern Vietnam associated with decreased human fatality rates, but increased human-to-human transmission.  This motif has been seen in 2003 isolates from Hong Kong and Yunnan, as well as 2004 isolates from Yunnan and Japan.

These differences in the HA cleavage site demonstrate how these motifs can recombine with various H5N1 HA genes circulating in Asia.  This recombination recycles old mutations into new combinations, and as seen by the four Guangdong isolates described above, these various motifs can co-circulate in a geographically small region, which generate new bird flu recombinants, such as the 2005 HA recombinant in northern Vietnam, which is expanding its host range to more efficiently infect humans.

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