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Pandemic Bird Flu - Recombination in Northern Vietnam

Recombinomics Commentary

April 23, 2005

>> Officials said the drop in the bird flu mortality rate was more marked in northern Vietnam than in the south. While the virus in southern Vietnam is still killing at the same pace as last year, the rate in the area around Hanoi and elsewhere in the north has dropped from that level to as low as 20 percent. Vietnamese health experts said their suspicion that the disease is shifting is further supported by preliminary research showing a genetic change in the virus in the north resulting in the production of a protein with one fewer amino acids than in the south. <<

The genetic change above sounds like a one amino acid deletion in the hemagglutinin protein (HA).  Highly pathogenic avian influenza frequently has a stretch of polybasic amino acids between the HA1 and HA2 regions of the HA0 precursor.  The polybasic amino acids allow a number of different proteases to cleave the precursor, which is a requirement for viral entry.  The absence of one of these basic amino acids may reduce the virulence of the virus.  In the pandemic viruses under vaccine development, polybasic amino acids in the region are removed to reduce the pathogenicity of the virus.

At the end of 2003, ducks being smuggled from Shanghai to Quemoy Island were confiscated and H5N1 isolated.  The sequences of all eight genes were deposited at Gen Bank as A/duck/China/E319-2/03(H5N1).  It was closely related to the virus subsequently isolated from a number of Asian countries, including Vietnam and Thailand. However, it was missing the nucleotides which encoded one of the basic amino acids.  Subsequently, isolates missing this one amino acid were also isolated from ducks in 2003 from Hunan (A/Dk/HN/5806/2003(H5N1), Yunan (A/Dk/YN/
6255/2003(H5N1) and A/Dk/YN/6445/2003(H5N1)), and in 2004 from a pheasant (A/Ph/ST/44/2004(H5N1)) in Shantou Province in China.

Vietnam has not made any of the sequences of H5N1 isolates from this season public.  However, it sounds like the virus in the north has the missing amino acid, suggesting it was formed via recombination with one of the isolates from China.  Since none of the prior publicly available sequences from Vietnam were missing this amino acid, it is likely that the newer version is a recombinant with an isolate from China.  This result suggests there is more recombination. It also suggests that there is more H5N1 in China than has been disclosed.  All of the China sequences at GenBank with the missing amino acid were isolated in 2003, except one isolate from 2004.  However, it was from last season and the sequence was deposited at GenBank in June of 2004.

Thus, the new sequence information suggests the 2005 isolates from northern Vietnam are less virulent and are recombinants with isolates from China.  These have not been deposited at GenBank and probably not disclosed.  Thus, countries can continue issuing press releases denying human-to-human transmission, or fail to report H5N1 to OIE, but H5N1 continues to recombine and evolve, with or without regard to scandalous monitoring and reporting.

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