Thursday, November 17, 2005

Crystal ball becomes cloudier still

The H5N1 virus, like all influenza viruses, has a natural tendency to mutate. There are a variety of mechanisms whereby this can happen. In the not so distant past one of the worrisome scenarios was that human and bird viruses would co-infect pigs and mix and match their genes to produce some hybrid of the worst of human and bird influenza viruses, the so-called reassortment mechanism. Then it become plausible that the virus didn't need to mix and match whole segments but might swap pieces of genes, either between its own gene segments (non-homologous recombination) or among the same genes from another viral strain or subtype co-infecting the cell (homologous recombination). This recombination mechanism has been championed by Henry Niman at Recombinomics. Long disparaged by flu researchers as a minor mechanism, it may turn out to be one of the principal drivers of genetic variation. Or maybe not. Then there is random mutation, the so-called genetic drift that viruses do on a daily or hourly basis when they replicate unfaithfully. We now believe that the kinds of genetic alternations needed to cause major changes in host range or virulence may be rather small and not require the kinds of wholesale substitutions the reassortment and recombination mechanisms use for the emergence of a pandemic strain.

And now the specter of reassortment is back with us with the announcement by Vietnamese scientists that other influenza subtypes, specifically H3 and H4 are circulating in poultry along with H5.
"The presence of more subtypes of the flu virus in poultry make the virus all the more dangerous," [Regional Animal Health Centre director Dong Manh] Ha said, adding that samples had been sent to a World Organisation for Animal Health (OIE) laboratory in Australia for further investigation.

State media reports said the new virus strains are H3N4 and H4N5. (Reuters)
Fourteen of Vietnam's 64 provinces now have designated bird flu outbreaks. In the last century, human influenza infections have been almost entirely subtypes H1N1, H2N2 and H3N2 but sporadic human cases with avian flu subtypes H5, H7 and H9 have occurred, the most virulent being the H5N1 that is currently the focus of concern. Now that H3 and H4 viruses are co-infecting birds that also have H5N1, we see entirely new opportunities for genetic combinations in animals in close proximity to humans. What the result of this will be no one knows. Maybe it has been going on for a long time and nobody bothered to look for the other subtypes, which cause generally milder disease in birds. Maybe not.

The situation can best be described as unpredictable. But you knew that.