Influenza viruses flow across the globe each flu season from a flu reservoir, probably in East and Southeast Asia, say two new studies that try to answer a question that has long puzzled the scientific and medical communities: Where does flu come from?
The scientific papers, released simultaneously by the heavy-hitting journals Science and Nature, suggest viruses that circulate during a North American or European winter don't lurk about waiting to pounce again the next fall when temperatures plummet. Instead, new waves of viruses invade from the source region.
Figuring out the dynamics of influenza evolution and spread should help flu experts project with more reliability which viruses are going to be next year's disease threat. Improving the ability to predict what's coming should lead to more accurate selections of strains for the annual flu shot, experts say.
Those involved in selecting strains for flu vaccine typically looked to see what was circulating at the tail end of the opposite hemisphere's influenza season to predict what is ahead.
"But now we know from this epidemiological-evolutionary study that it's all coming from the tropical region,'' said Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, one of the National Institutes of Health. The NIH supported both pieces of research.
"I think this will give us scientific reason to mine more carefully and extensively into the tropical regions.''
The Nature study, from researchers at Pennsylvania State University and the NIH, looked at full genetic sequences of about 1,300 influenza A viruses collected primarily in New York State and New Zealand.
Senior author Eddie Holmes of Penn State said the work is probably the largest full-genome study of a virus ever done.
By tracking the evolutionary changes in the viruses' genes, they suggest a so-called "sink-source model'' of evolution and spread. But because they were looking exclusively at viruses from temperate zones in the Northern and Southern hemisphere, they can only hypothesize that the source is in the tropics and probably Asia.
The Science paper, by a who's who of flu experts, looked at the critical hemagglutinin gene of more than 13,000 human H3N2 viruses from around the globe.
The work, led by researchers from the pathogen evolution group in Cambridge University's zoology department, suggests flu viruses are constantly evolving, emerging and spreading among unnamed countries of East and Southeast Asia.
Successful viruses -- those that are able to evade the immune systems of lots of people -- then spread from that reservoir to North America, Europe and Australia and New Zealand. South America eventually gets hit by viruses that have spread from Europe and North America. Flu spread in Africa has so far been too little studied to say how it fits into the picture, the authors say.
These authors suggest the route viruses take is essentially a one-way street: Viruses from North or South America don't wend their way back to Asia to start new waves of infection there.
Abstract:
The genomic and epidemiological dynamics of human influenza A virus
Andrew Rambaut, Oliver G. Pybus, Martha I. Nelson, Cecile Viboud, Jeffery K. Taubenberger & Edward C. Holmes
The evolutionary interaction between influenza A virus and the human immune system, manifest as 'antigenic drift' of the viral haemagglutinin, is one of the best described patterns in molecular evolution. However, little is known about the genome-scale evolutionary dynamics of this pathogen. Similarly, how genomic processes relate to global influenza epidemiology, in which the A/H3N2 and A/H1N1 subtypes co-circulate, is poorly understood. Here through an analysis of 1,302 complete viral genomes sampled from temperate populations in both hemispheres, we show that the genomic evolution of influenza A virus is characterized by a complex interplay between frequent reassortment and periodic selective sweeps. The A/H3N2 and A/H1N1 subtypes exhibit different evolutionary dynamics, with diverse lineages circulating in A/H1N1, indicative of weaker antigenic drift. These results suggest a sink-source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions.
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