Researchers map 209 flu virus genomes

Oct 6, 2005 (CIDRAP News) – Influenza researchers marked a milestone yesterday by publishing a report on the complete genetic mapping of 209 samples of human flu viruses, vastly increasing the supply of genetic data on flu.

The report, published in Nature, is one of the first fruits of the Influenza Genome Sequencing Project, which aims to trace the genetic blueprints of thousands of flu viruses. The project, announced in November 2004, is a joint effort of the National Institute of Allergy and Infectious Diseases (NIAID), the National Center for Biotechnology Information, the Wadsworth Center of the New York State Department of Health in Albany, and The Institute for Genomic Research (TIGR) in Rockville, Md.

"These new data give us the most comprehensive picture to date of how influenza viruses evolve and are transmitted throughout human populations," NIAID Director Anthony Fauci, MD, said in a news release. He said the new information could lead to better vaccines, drugs, and diagnostic tools for flu.

The research was done by a large team, with Elodie Ghedin of TIGR listed as the first author. They published their report the same day other teams reported on the re-creation of the deadly 1918 pandemic flu virus and a finding that the 1918 virus closely resembled avian flu viruses.

Ghedin and colleagues say that until now, scientists had fully mapped and published the genomes of only a few strains of human flu viruses. Most of the published data pertain to short fragments of the genes for the virus's two key surface proteins, hemagglutinin and neuraminidase.

"As a result of this project, the number of complete human H3N2 influenza virus genomes in GenBank [a public online database] has already grown from just seven genomes to over 200," the article says.

The samples analyzed include 207 H3N2 viruses and two H1N2 isolates, which were gathered in New York state over five flu seasons, from 1998-99 through 2003-04. "The sequenced strains were not preselected because of their virulence or unusual characteristics, giving researchers an unbiased view of flu virus evolution as it moved through a varied human population," the NIAID statement said.

The viruses were surprisingly varied. "Even within a geographically constrained set of isolates, we have found surprising genetic diversity, indicating that the reservoir of influenza A strains in the human population—and the concomitant potential for segment exchange between strains—may be greater than was previously suspected," the researchers write.

They detected a number of mutations (changes in particular amino acids) that occurred during the study period, and also found three cases in which strains traded whole gene segments (reassortments).

In July some members of the team reported in detail on the most significant of these events, in which two groups, or clades, of H3N2 viruses acquired the hemagglutinin gene from a third H3N2 group. That gave rise to the Fujian strain of flu, which predominated in the 2003-04 flu season. The vaccine that year was not well matched to the Fujian strain and had reduced effectiveness.

By carefully cataloging mutations and reassortments, "we can begin to get the first real picture of the rate of mutational events underlying influenza A virus evolution," the researchers write.

The flu genome sequencing project is now being expanded to include avian flu, in an effort to learn how often avian strains cross into humans, the article says. The H5N1 avian strain now circulating in Asia has already infected more than 115 humans. Experts fear it could soon gain the ability to spread readily from person to person, thereby launching a pandemic.

Ghedin E, Sengamalay NA, Shumway M, et al. Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution. Nature 2005 Oct 5 (advance online publication) [Full text]

See also:

Jul 26, 2005, CIDRAP News story "Flu viruses can evolve in unsuspected ways, study says"

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