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Mutation altering stability of surface molecule in acid enables H5N1 infection of mammals
Date:2/28/2013

infect ducks. Noting that the upper airways of mammals are more acidic than infected tissues of birds, they hypothesized, correctly, that a mutation rendering the hemagglutinin protein resistant to acid might render the virus more infective in mammals.

In this study the investigators found that K58I grows 100-fold better than the wild-type in the nasal cavities of mice, and is 50 percent more lethal. Conversely, the mutant K58I virus failed completely to kill ducks the investigators infected, while the wild-type killed 66 percent of ducks, says Russell. "A single mutation that eliminates H5N1 growth in ducks simultaneously enhances the capacity of H5N1 to grow in mice. We conclude that enhanced resistance to acid inactivation helps adapt H5N1 influenza virus from an avian to a mammalian host."

"These data contribute new information about viral determinants of influenza virus virulence and provide additional evidence to support the idea that H5N1 influenza virus pathogenesis in birds and mammals is linked to the pH of [hemagglutinin] activation in an opposing fashion," Terence S. Dermody of Vanderbilt University et al. write in an editorial in the journal accompanying the paper. "A higher pH optimum of [hemagglutinin] activation favors virulence in birds, whereas a lower pH optimum favors virulence in mammals."

Based on this and another study, "surveillance should include phenotypic assessment of the [hemagglutinin] activation pH in addition to sequence analysis," Dermody writes.

The journal carefully considered whether to publish the paper, because it raised issues of "dual use research of concern" (DURC), writes Dermody. DURC is defined as "Life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultura
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Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

Page: 1 2 3

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