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NIH grantees rebut theory that seasonal flu strains originate in tropical regions

Influenza researchers have found that flu strains migrate back and forth between different regions of the world, evolving along the way. This is contrary to the common belief that flu strains from the tropics are the source of global seasonal epidemics.

The research appeared online on Nov. 14 in the Proceedings of the National Academy of Sciences. It was supported in part by the Centers of Excellence for Influenza Research and Surveillance and the Influenza Genome Sequencing Project, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

"This study helps us to better understand why the persistence, movement and evolution of flu viruses are complex and largely unpredictable," said NIAID Director Anthony S. Fauci, M.D. "These findings also remind us of the importance of maintaining vigilance in our global influenza surveillance efforts."

Previous studies had shown that in general, influenza viruses in tropical regions tend to be more varied and circulate year-round rather than seasonally, like flu viruses found in temperate regions with more moderate climates. The prevailing theory had been that tropical areas of the world may be the source of flu viruses from which new seasonal flu strains originate.

To test this theory, researchers led by Justin Bahl, Ph.D., and Gavin J.D. Smith, Ph.D., of the Duke-National University Graduate Medical School in Singapore, genetically analyzed strains of H3N2 influenza virus, a common cause of seasonal influenza among humans, collected between 2003 and 2006. They sequenced the full genome of 105 flu virus samples from Hong Kong and compared these with H3N2 virus sequences obtained from seven geographic areas with varying climates, including five temperate regions (Australia, Europe, Japan, the United States, and New Zealand) and two tropical regions (Hong Kong and Southeast Asia). The strains were arranged into a phylogenetic, or family, tree, showing the relationships between the strains and how they evolved over time.

"Earlier genetic studies had looked at H3N2 in a global context and concluded that new strains came from the tropics," said Dr. Bahl. "However, in those studies, a lot of key genetic data from the tropics was missing." This made it difficult to draw a firm conclusion about the origin of new flu strains, he said.

The researchers found that in temperate regions where flu seasons are relatively short, many new H3N2 virus strains arise every year, but they rarely persist from one season to the next. However, in Hong Kong and Southeast Asia, where flu seasons occur for longer periods of time, strains do persist between seasons.

Keeping these patterns in mind, the investigators traced the geographical movement of the strains to determine whether new flu strains actually originate in tropical regions. Instead, they found that influenza strains frequently migrate back and forth between tropical and temperate regions, and that the tropical regions were not necessarily the source of new strains.

In fact, none of the seven temperate and tropical regions they examined was the source of all new H3N2 flu strains in a given year. The migration pattern was more complex. Virus strains moved from one region to several others each year, and flu outbreaks were traced back to more than one source. And although the virus that migrated between Southeast Asia and Hong Kong persisted over time, its persistence was caused by the introduction of virus from the temperate regions. Therefore, the tropical regions did not maintain a source for the annual H3N2 influenza epidemics. Further, in contrast to annual flu epidemics in temperate climates, relatively low levels of genetic diversity among flu strains and no seasonal fluctuations were found in the 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," said Dr. Bahl. "Regions with more connections to others, such as travel centers, may contribute more to the global diversity of circulating viruses."

The complexity of the global virus circulation found in the study suggests that efforts to control flu should include region-specific strategies, according to the researchers. In future studies, the researchers intend to examine whether the virus behaves differently in temperate and tropical areas, including regions not included in this analysis, and in places that are more or less connected to the rest of the world.


Contact: Nalini Padmanabhan
NIH/National Institute of Allergy and Infectious Diseases

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