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Science Study Helps to Unravel the Origins of the New H1N1 Flu Virus

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By sequencing the genomes of more than 50 samples of the new A(H1N1) influenza virus, researchers have found that it is distantly related to its nearest relatives, indicating that its genes have been circulating undetected for an extended period. The findings suggest that in the future pig populations will need to be closely monitored for emerging influenza viruses.

Completed by an international team of investigators from the United States, the United Kingdom and Mexico, the research was made available for immediate release 22 May 2009, following acceptance by Science. Journal editors provided free public access to the findings, in light of public health concerns regarding the A(H1N1) virus.

The research team including lead Science authors Rebecca J. Garten and C. Todd Davis of the World Health Organization Collaborating Center for Influenza, Centers for Disease Control and Prevention sequenced the full or partial genomes of 2009 A(H1N1) viruses isolated in Mexico and the United States. They determined the origins of the virus eight gene segments and found that the combination of these gene segments has not previously been reported among swine or human influenza viruses.

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Figure 1 from the 22 May 2009 Science paper by Rebecca J. Garten and colleagues illustrates the origin of the gene segments of the novel A(H1N1) influenza virus: PB2, or polymerase basic 2; PB1, or polymerase basic 1; PA, polymerase acidic; HA, hemagglutinin; NP, nucleoprotein; NA, neuraminidase; MP, matrix protein; and NS, nonstructural protein. The color of the gene segment in the circle indicates the host. (Reference, DOI: 10.1126/science.1176225.)

All of the segments originated in avian hosts and then began circulating in pigs at various times in history, from 1918 through to 1998. Six of the eight segments originated from triple reassortant swine viruses which include genetic material from human, avian and swine viruses as the result of these viruses tendency to swap pieces of their genomes with each other that have been circulating in North America and Asia since approximately1998.

The other two segments are derived from Eurasian swine viruses. The sequences for the gene segments did not reveal the signatures of high transmissibility or virulence that have been found in other influenza A viruses, suggesting that other, yet-unknown sequences are responsible for the new virus  ability to replicate and spread in humans.

The researchers also took a closer look at the new A(H1N1) virus  hemagglutinin protein, which is responsible for the virus  ability to bind to and infect its host cell. Test-tube experiments that examined how ferret antibodies reacted against this protein suggest that the new strain has antigenic properties that are similar to those of other swine A(H1N1) viruses but distinct from seasonal human flu. Researchers will need to continue to look for changes in the hemagglutinin protein in the new virus, which may affect the selection of vaccine candidates, the authors say.

The Science paper is entitled Antigenic and Genetic Characteristics of a Novel A (H1N1) Influenza Virus Circulating in Humans. (Reference, DOI: 10.1126/science.1176225.)