In the first large-scale effort of its kind, researchers have determined the full genetic sequence of more than 200 distinct strains of human influenza virus.
The information, being made available in a publicly accessible database, is expected to help scientists better understand how flu viruses evolve, spread and cause disease. The genomic data already has enabled scientists to determine why the 2003-4 annual influenza vaccine did not fully protect individuals against the flu that season.
The new genomes are the initial results of the Influenza Genome Sequencing Project, a joint effort of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and multiple partners including NIH's National Center for Biotechnology Information (NCBI), the Wadsworth Center of the New York State Department of Health in Albany, NY, and The Institute for Genomic Research (TIGR) in Rockville, MD. The report was published online in the journal Nature on October 5.
"These new data give us the most comprehensive picture to date of how influenza viruses evolve and are transmitted throughout human populations," says NIAID Director Anthony S. Fauci, M.D. "This information could help us to make more effective vaccines, therapeutics and diagnostics against a disease that claims some 36,000 American lives each year."
The scientists, led by Elodie Ghedin, Ph.D., of TIGR, and Steven Salzberg, Ph.D., of the University of Maryland, College Park, fully sequenced 209 strains of flu virus, determining the order of more than 2.8 million nucleotide bases, the building blocks of DNA. Until now, the researchers note, most of the gene sequence information available to scientists comprised only relatively short fragments of flu genes that encode two of the virus' key surface proteins, hemagglutinin (H) and neuraminidase (N). In collaboration with David Lipman, M.D., and colleagues at NCBI, NIAID will rapidly make this sequence information publicly available through GenBank®, an international, searchable online database.
This was the first large-scale effort to sequence flu strains drawn at random from a geographically limited region: most strains came from samples submitted over five years to the New York State Department of Health. The sequenced strains were not pre-selected for virulence or other characteristics, giving researchers an unbiased view of flu virus evolution as it moved through a varied human population.
Although the viruses were drawn from a relatively small region, the researchers discovered a surprisingly large degree of genetic diversity in the sequences. They learned, for example, that three genetically distinct variants of the dominant H3N2 strain appeared over the study period. In some seasons, these variants circulated simultaneously; New York residents were suffering from similar, but distinct, versions of the virus.
With this new, highly detailed genomic information, the researchers found out why the 2003-04 flu vaccine provided only partial protection against that season's flu. During the 2002-03 season, distinctly different versions of the H3N2 flu virus underwent genetic mixing. The resulting strain emerged late in the season and became the predominant cause of flu the following year. However, the 2003-04 vaccine did not target the late-emerging version of H3N2 and so the vaccine provided less than optimal protection. In the future, say the researchers, rapid sequencing of flu strain variants could provide information needed to craft vaccines precisely tailored against the most virulent strains.
"Through the Influenza Genome Sequencing Project, techniques have been established to allow rapid sequencing of full genomes of influenza virus. This project continues to move toward our goal of revealing complete genetic blueprints of thousands of known human and avian influenza viruses over the next several years," says Maria Y. Giovanni, Ph.D., who oversees NIAID's flu genome sequencing project.