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2005 H5N1 Reassortment and Recombintion at Qinghai Lake
July 6, 2005
>> Sequence comparison revealed that the H5N1 viruses were almost identical across all gene segments. The haemagglutinin gene retains the motif of basic amino acids (QGERRRKKR) in the connecting peptide that characterizes highly pathogenic avian flu. All Qinghai isolates had a Lys 627 mutation in the PB2 gene, which has been associated with increased virulence in mice4. Phylogenetic analysis of these isolates and eight other H5N1 viruses, isolated from poultry markets in Fujian, Guangdong, Hunan and Yunnan provinces during 2005, indicated that the haemagglutinin (Fig. 1a), neuraminidase and nucleoprotein (data not shown) genes of the Qinghai viruses were closely related to the H5N1 virus A/Chicken/Shantou/4231/2003 (genotype V).
However, the other five internal genes, represented by the matrix-protein gene, were closely related to H5N1 viruses isolated from domestic poultry in southern China during 2005, represented by the virus A/Chicken/Shantou/810/2005 (genotype Z) (Fig. 1b). These viruses are therefore characterized as H5N1 genotype Z, but are clearly distinguishable from those that have caused human infection in Thailand and Vietnam (Fig. 1a, b)5. This indicates that the virus causing the outbreak at Qinghai Lake was a single introduction, most probably from poultry in southern China. <<
The above comments from tomorrow's Nature raise several concerns. The H5N1 bird flu isolates from Qinghai Lake are similar to each other, indicating a common source. The isolates are reassortants, which signals more dual infections and almost certainly more recombination. Although three of the genes are very closely related the Shantou isolates, there is no data on H5N1 in India, other than three poultry worker's antibodies from 2002.
The initial bird deaths at Qinghai Lake were bar headed geese, which winter in India. Thus it is possible that bar headed geese brought the genes to Qinghai Lake previously, and migrating birds brought those sequences to Shantou. More analysis of the sequences at GenBank may provide some clues on the direction of the migration. However, the latest version of H5N1 appears to be quite lethal to several species of migratory birds. The PB2 627 mutation is present in some of the more lethal version of H5N1 in Vietnam and Thailand, so this change could spread significantly by the migrating birds
Clearly the H5N1 situation in Asia is spinning out of control and China is becoming less transparent. The Nature report lists 8 new 2005 isolates and the accession numbers suggest 20 isolates will become available at GenBank. Based on the discussion, it seems likely that all 20 isolates are from China. In the May 21 OIE report, China described the death of 519 migratory birds from 5 species. These are probably represented by isolates A/Bar-headed Gs/QH/5/05, A/GSH gull/QH/2/05, A/BH gull/QH/3/05, and A/Bar-headed Gs/QH/12/05.
The phylogenetic placement of the other H5N1 isolates from Chian would indicate they are HPAI, which is a reportable disease to OIE. However, other than the three OIE reports on birds in Qinghai and Xinjiang, there are no reported H5N1 outbreaks in China in 2005, although figure 1 lists 2005 isolates from Hunan (DK/HN/114/05), Yunnan (Ck/YN/493/05) and Shantou (A/Ck.ST/810/05, A/Gs/ST/1621/05). China has also indicated limitations of studying healthy birds and exporting of samples has been implemented, limiting further study of H5N1 inside China.
However, H5N1 will be flying out of China into neighboring countries in the near term.