Recombinomics: Unstable Clade 7 H5N1 In China Raises Concerns

Commentary

Recombinomics Commentary 10:34
March 30, 2009

A recent clade 7 HA sequence from a chicken in Vietnam, A/chicken/Vietnam/NCVD-03/2008 was released at Genbank under the title, "Characterization of a highly pathogenic avian influenza H5N1 sublineage in poultry seized at ports of entry into Vietnam". It was proposed as a vaccine target in the recent WHO update because it was antigenically distinct from another recent clade 7 target, A/chicken/Vietnam/NCVD-016/2008, which was isolate in northern Vietnam near the border with China. Both of these sequences have a cleavage site similar to clade 7 isolated in 2006 in China, except the cleavage site has a 3 BP insertion, encoding for an additional basic amino acid.

However, the recent sequence also has a duplication of sequences encoding the two amino acids at the beginning of the cleavage site, creating the novel cleavage site, REREGGRRRKR. The sequence also has an addition 3 BP deletion, which is distinct from the 3 BP deletion found in earlier clade 7 isolates from China, as well as clade 2.2 isolates in Egypt.

The selection of two 2008 clade 7 targets from Vietnam is unusual, but follows a spate of cases in China in January. These cases followed confirmed clade 7 outbreaks in poultry in Jiangsu in December, 2008 and strongly suggest that most of the human cases in China were clade 7.

The sequences form these patients have not been released and have only been described in general terms in reports from China. The WHO report was silent on all cases from China except for two that were the Fujian strain (clade 2.3.2 and 2.3.4), further supporting concerns that vaccine resistant clade 7 is widely circulating in China.

The recent sequences from northern Vietnam demonstrate considerable genetic instability that involves a large number of non-synonymous changes as well as insertions and deletions in the HA sequence.

Release of sequences from the Jiangsu poultry outbreaks in China, as well as recent human cases in China and northern Vietnam would be useful.

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