An international research team has shown how changes in an influenza virus that has plagued poultry farms in China for decades helped create the novel avian H7N9 influenza A virus that has sickened more than 375 people since 2013.

The research appears in the current online early edition of the scientific journal Proceedings of the National Academy of Sciences.

The results underscore the need for continued surveillance of flu viruses circulating on poultry farms and identified changes in the H9N2 virus that could serve as an early warning sign of emerging flu viruses with the potential to trigger a pandemic and global health emergency, an announcement from the St. Jude Children's Research Hospital said.

The work focused on the H9N2 chicken virus, which causes egg production to drop and leaves chickens vulnerable to deadly co-infections. Scientists at St. Jude's and the China Agricultural University in Beijing led the study.

Researchers used whole genome sequencing to track the evolution of the H9N2 chicken virus between 1994 and 2013. The analysis involved thousands of viral sequences and showed that the genetic diversity of H9N2 viruses fell sharply in 2009. From 2010 through 2013, an H9N2 virus emerged as the predominant subtype due to its genetic makeup that allowed it to flourish despite widespread vaccination of chickens against H9N2 viruses.

Evidence in this study suggests the eruptions set the stage for the emergence of the H7N9 avian virus that has caused two outbreaks in humans since 2013, with 115 confirmed deaths. The H9N2 infected chickens likely served as the mixing vessel where H9N2 and other avian flu viruses from migratory birds and domestic ducks swapped genes, the researchers noted. The resulting H7N9 virus included six genes from the H9N2 virus.

"Sequencing the viral genome allowed us to track how H9N2 evolved across time and geography to contribute to the H7N9 virus that emerged as a threat to human health in 2013," said Dr. Robert Webster, a member of the St. Jude department of infectious diseases. He and Dr. Jinhua Liu of the College of Veterinary Medicine at the China Agricultural University, are co-corresponding authors.

"The insights gained from this collaboration suggest that tracking genetic diversity of H9N2 on poultry farms could provide an early warning of emerging viruses with the potential to spark a pandemic," Webster said.

The analysis also provided insight into the creation of the H9N2 virus that emerged as the predominant subtype in 2010. Factors included widespread use of poultry vaccines and the natural tendency of flu to mutate, mix and swap genes.