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Recombination of H5N1 in Vietnam is Serious
May 11, 2005
>> With so few samples to work on, it is impossible to judge how worried to be, says Klaus Stöhr, coordinator of the WHO's flu programme. "It's as if you hear a noise in your car engine, but you keep driving, not knowing whether it's serious."
Of the six human samples that the WHO has received from Vietnam, several contain a mutated version of H5N1. But that is not enough to indicate a broader change in the strain, says Perdue. It is also impossible for the agency to link this mutation of the virus to possible changes in how pathogenic and transmissible it is in humans. <<
Although more 2005 samples would be useful, the fact that several contain a mutated version of H5N1 would seem to be significant. The database for 2004 isolates from Vietnam, Thailand, and several other countries in Asia is large, and it is reinforced with a large number of H5N1 sequences from isolates of this decade.
The main problem is not the amount of data, but the interpretation of data. The existing database has ample evidence for recombination as the principle driver of H5N1 evolution. However, the WHO is still talking about mutations and reassortment, when the real genetic change is driven by recombination.
As noted above, the 2005 genes have changed. Genes do not change via reassortment, which merely shuffles existing genes. The Z genotype is defined by reassortment, and the vast majority of the current H5N1 isolates are the Z genotype, including isolates from Japan, Korea, Indonesia and many provinces in China. These H5N1 isolates have not been reported to cause fatal human infections. However, the Z genotypes in Vietnam and Thailand have caused infections with a high case fatality rate. It is the region-specific differences in the genes that are associated with the reported fatal infections in humans.
These differences are generated via recombination. The new 2005 isolates missing one amino acid are almost certainly recombinants between H5N1 isolates from Vietnam and China.
More data would be useful, but widespread infections of diverse H5N1 that are continually changing via recombination are serious, no car mechanic required.