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Increased Genetic Diversity in HPAI H5N1

Recombinomics Commentary

December 21, 2005

Biological tests on dead and sick poultry from the Crimea showed the birds were infected with the H5N1 strain genetically similar to the Yokogama, Qinghai, Yunhan and Shantou strains

The above comments on the genetics of the H5N1 isolates for Ukraine suggests the wild bird version is rapidly evolving.  The novel wild bird sequences were first reported from isolates from Qinghai Lake in May 2005.  Those sequences share polymorphisms with isolates from eastern China, Japan, and South Korea.  However the isolate from Yokohama was from duck meat being smuggles into Japan from northern China.  That sequence was distinct from the sequences at Qinghai Lake, although there were some polymorphisms that were found in those sequences.  The current description of the Ukraine sequence suggests more Yokohama sequences have been acquired.

The acquisition of novel sequences has become clearer as more sequences from 2005 are published.  Three isolates from whooper swans in Mongolia have a novel HA cleavage site and now the sequence from an outbreak in Hunan also has a novel HA cleavage site that is a combination of the site from Mongolia and the sequences from northern China that have dropped a lysine (K).

These novel HA cleavage site signal more rapid change in H5N1 as it expands its global reach, and highlight the need for more surveillance and sequences.

The number of 2005 sequences made available at GenBank is significant below 2004.  There are still no complete sequences from Vietnam or Cambodia and the number of sequences from Thailand has also been minimal.  There are no bird or human sequences available from Indonesia and China has not deposited human sequences.

Clearly more aggressive surveillance is required and more sequences should be deposited more quickly.

However, WHO and media reports indicate that H5N1 is rapidly evolving and the number of versions that can infect humans is steadily increasing.  In 2004 two slightly different versions of clade 1 of the Z genotype were isolated from patients in Vietnam and Thailand.  In early 2005, many of the isolates in Vietnam, including those from patients, had lost a K in the HA cleavage site.  Later this year the first cases of H5N1 in humans were reported in Indonesia.  Sequence analysis of those isolates indicated they were similar to clade 2 isolates from Indonesian poultry.  Some media reports indicated that at least two versions of clade 2 were co-circulating.

More recently China described the first reported H5N1 human cases in Hunan.  Although H5N1 was not isolated directly from either patient, H5N1 was isolated from a family chicken and it was similar to clade 2 H5N1 from Fujian province and had a novel HA cleavage site.  China has reported five additional cases in for additional provinces.  These other cases were linked to poultry outbreaks linked to migratory birds, suggesting more variations will be reported.

Thus, the rapid evolution of H5N1 worldwide as well as in versions that can cause human infections dictates a rapid deposit of sequences in public databases.  The flu season in the northern hemisphere will almost certainly lead to dramatic increases and variation of H5N1 sequences as the number of dual infections and recombinants increase.


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