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International Team Publishes Swine Flu Genetic Analysis

NEW YORK (GenomeWeb News) – The influenza A H1N1 virus — commonly referred to as swine flu — contains both "triple reassorted" human, bird, and pig flu gene segments as well as gene segments resembling those in Eurasian swine flu viruses, according to a paper appearing online today in Science.

An international research team from the US, UK, and Mexico obtained genome sequences from seven Mexican H1N1 viruses and nearly four dozen American viruses isolated this year. Their results suggest that viruses sampled from North America resemble one another but are distinct from previously reported swine flu viruses, containing six gene segments that are a jumble of human, bird, and pig flu viruses and two that are similar to Eurasian swine flu viruses.

"This novel A(H1N1) virus contains a combination of gene segments that previously has not been reported among swine or human influenza viruses in the United States or elsewhere," lead author Rebecca Garten, a researcher with the World Health Organization Collaborating Center for Influenza at the US Centers for Disease Control and Prevention, and her colleagues wrote.

A "classical" influenza A H1N1 swine flu was first identified in pigs in 1930. In the late 1990s, that virus seems to have combined with various human and bird flu viruses in North America and Asia.

In humans, meanwhile, influenza A H1N1 viruses circulated as the predominant seasonal flu strain from 1918 to the late 1950s. It was briefly replaced by H2N2, which caused a 1957 flu pandemic, but reappeared in the late 1970s. Between 1977 and 2009, human H1N1 viruses continued evolving, presenting a handful of new antigens that have subsequently been added to flu vaccines.

Although classical and recombined swine flu cases have been reported in humans in the past, the authors noted, these viruses couldn't move easily from one human to the next, limiting their spread. The new version of the H1N1 swine flu, on the other hand, has acquired human transmissibility. Since April of this year it has reportedly been detected in dozens of countries, causing at least 46 deaths.

In an effort to untangle the genetic and antigenic characteristics of this new strain, the researchers sequenced the partial or complete genomes of seven H1N1 viruses isolated in Mexico and 44 viruses isolated in 13 American states.

Their results indicate that the new H1N1 virus contains a combination of genes that hasn't been seen in pigs or humans. Of the virus' eight gene segments, six contain a mishmash of human, bird, and pig viral sequence. The other two regions are more similar to Eurasian swine flu viruses, which entered pig populations from birds in the late 1970s.

Because flu viruses are so prone to rearrangement, the researchers noted that the current strain may have been circulating in swine herds for some time but remained undetected due to a lack of extensive surveillance.

The researchers noted that the molecular underpinnings of human-to-human transmission by the virus appear to be distinct from those associated with the 1918 flu or the pathogenic H5N1 strain.

Despite the strain's differences from previously characterized flu viruses, the team noted that the new H1N1 viruses sequenced in North America so far are very similar to one another, though they detected four minor variants in the viral genomes.

The team also did a viral antigen analysis of the new strain. Results from those experiments suggest that the current H1N1 viral antigens are similar to classical swine flu viruses but dramatically different from seasonal flu viruses.

Health officials are expected to continue keeping tabs on the outbreak virus to determine whether it is taking on additional genetic or antigenic changes that could affect future treatment and prevention measures.

"Worldwide monitoring of the antigenic and genetic properties of the novel A (H1N1) viruses continues for, among other reasons, detecting any changes and thus any necessity for selecting further vaccine candidates," the authors noted. "Ongoing full genome sequencing will monitor for the possibility of future reassortment events."

H1N1 sequences are being continuously uploaded to the NCBI's Influenza Virus Resource site. Data on the antigenic features of the virus are also available online at the Antigenic Cartography site.