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Flu Phylogeny Points to Multiple Sources for Seasonal Outbreaks

NEW YORK (GenomeWeb News) – The influenza viruses behind seasonal outbreaks can stem from interactions between strains found in many populations and do not have a single tropical source, according to a study in the early, online version of the Proceedings of the National Academy of Sciences this week.

It was previously thought that tropical regions such as East Asia and Southeast Asia served as a source population for seasonal flu strains in more temperate parts of the world, since these strains tend to be diverse and circulate all year, while those in more temperate climes typically crop up seasonally.

But an international team led by investigators at the Duke-National University of Singapore Graduate Medical School came to a different conclusion when they sequenced more than 100 influenza A H3N2 isolates from Hong Kong and compared their sequences with those found in seasonal strains collected from other parts of the world between 2003 and 2006.

"Earlier genetic studies had looked at H3N2 in a global context and concluded that new strains came from the tropics," the study's first author Justin Bahl, a Duke-NUS researcher who is also affiliated with China's State Key Laboratory of Emerging Infectious Diseases, said in a statement. "However, in those studies, a lot of key genetic data from the tropics was missing."

By analyzing sequence information from more than 1,000 isolates from seven parts of the world, Bahl and his colleagues found that H3N2 influenza strains in the tropical regions tested — Hong Kong and Southeast Asia — showed relatively little genetic change from one flu season to the next. Nevertheless, these strains seemed to be influenced by strains circulating in temperate regions, they found, with seasonal strains apparently stemming from multiple sources and moving to and from tropical regions.

"We found that the H3N2 influenza virus population is constantly moving between regions, and every region is a potential source for new epidemics," Bahl said. "Regions with more connections to others, such as travel centers, may contribute more to the global diversity of circulating viruses."

"This study helps us to better understand why the persistence, movement and evolution of flu viruses are complex and largely unpredictable," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in a statement. "These findings also remind us of the importance of maintaining vigilance in our global influenza surveillance efforts."

For the study, which was partly funded through NIAID's Centers of Excellence for Influenza Research and Surveillance and the NIAID Influenza Genome Sequencing Project, researchers did phylogenetic analyses involving 105 newly sequenced H3N2 isolates from Hong Kong and roughly 1,200 isolates from other parts of the world that were found in sequence databases.

Isolates included in the analysis had been collected in Europe, Australia, New Zealand, Japan, New York, Hong Kong, and Southeast Asia between 2003 and 2006. The Southeast Asian isolates included samples from Cambodia, Indonesia, Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam.

From their analyses of HA1 domain and other sequences, the team saw phylogenetic clustering by region that was consistent with seasonal flu outbreaks.

But the relationships between isolates from different parts of the world were not consistent with a single East or Southeast Asian source for the seasonal flu strains found elsewhere. Instead, the complex patterns detected pointed to movement of H3N2 strains both into and out of the tropical regions tested.

Moreover, the genetic patterns pointed to multiple sources for the seasonal flu strains, researchers noted, explaining that "the global persistence of H3N2 influenza A virus is the result of a migrating meta-population in which multiple different localities may seed seasonal epidemics in temperate regions in a given year."

"Such complex global migration dynamics may confound efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses," they added.

Based on their findings, the study authors argued that incorporating information at a regional level may help in improving flu surveillance and vaccine selection approaches.

"Current strategies for the control of influenza by vaccination are based on the biannual selection of vaccine candidates for the Northern and Southern hemispheres and require an understanding of genetic and antigenic variants circulating and the potential for new variants to emerge," they explained.

"Although such actions represent an effective vaccine strategy in temperate regions, the complex global dynamics we observe suggest that efforts to control influenza should include region-specific strategies to advance the current global policy."

For its part, the team plans to extend their flu virus analyses to include strains from other locales and hopes to learn more the role that geographic factors play, if any, in flu virus evolution in tropical and temperate regions.

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