Mutation inquiétante du virus H5N1

Highly pathogenic avian H5N1 influenza A viruses have spread throughout Asia, Europe, and Africa, raising serious worldwide concern about their pandemic potential. Although more than 250 people have been infected with these viruses, with a consequent high rate of mortality, the molecular mechanisms responsible for the efficient transmission of H5N1 viruses among humans remain elusive. We used a mouse model to examine the role of the amino acid at position 627 of the PB2 viral protein in efficient replication of H5N1 viruses in the mammalian respiratory tract. Viruses possessing Lys at position 627 of PB2 replicated efficiently in lungs and nasal turbinates, as well as in cells, even at the lower temperature of 33 8C. Those viruses possessing Glu at this position replicated less well in nasal turbinates than in lungs, and less well in cells at the lower temperature. These results suggest that Lys at PB2–627 confers to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. Therefore, efficient viral growth in the upper respiratory tract may provide a platform for the adaptation of avian H5N1 influenza viruses to humans and for efficient person-to-person virus transmission, in the context of changes in other viral properties including specificity for human (sialic acid a-2,6-galactose containing) receptors. Citation: Hatta M, Hatta Y, Kim JH, Watanabe S, Shinya K, et al. (2007) Growth of H5N1 influenza A viruses in the upper respiratory tracts of mice. PLoS Pathog 3(10): e133. doi:10.1371/journal.ppat.0030133 Introduction The first outbreak in humans caused by the highly pathogenic H5N1 influenza A virus was reported in Hong Kong in 1997, and resulted in the deaths of six of 18 infected people [1–3]. This event demonstrated for the first time the direct transmission of a highly pathogenic avian influenza virus from birds to humans with a fatal outcome. In December 2003, this virus began to spread widely in poultry in Vietnam, Indonesia, and Thailand and has since spread to countries in the Middle East, Europe, and Africa, resulting in huge economic losses in the poultry industries of the affected regions. More than 250 human infections have been identified, of which more than 150 have been fatal [4], raising serious worldwide concern about a catastrophic influenza pandemic. Fortunately, efficient human-to-human transmission of this virus has not yet occurred, lending impetus to efforts to identify the molecular mechanisms that

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