In the first large-scale effort of its kind, researchers havedetermined the full genetic sequence of more than 200 distinct strainsof human influenza virus. The information, being made available in apublicly accessible database, is expected to help scientists betterunderstand how flu viruses evolve, spread and cause disease. Thegenomic data already has enabled scientists to determine why the 2003-4annual influenza vaccine did not fully protect individuals against theflu that season.
The new genomes are the initial results of the Influenza GenomeSequencing Project, a joint effort of the National Institute of Allergyand Infectious Diseases (NIAID), part of the National Institutes ofHealth (NIH), and multiple partners including NIH's National Center forBiotechnology Information (NCBI), the Wadsworth Center of the New YorkState Department of Health in Albany, NY, and The Institute for GenomicResearch (TIGR) in Rockville, MD. The report was published online inthe journal Nature on October 5.
"These new data give us the most comprehensive picture to date of howinfluenza viruses evolve and are transmitted throughout humanpopulations," says NIAID Director Anthony S. Fauci, M.D. "Thisinformation could help us to make more effective vaccines, therapeuticsand diagnostics against a disease that claims some 36,000 Americanlives each year."
The scientists, led by Elodie Ghedin, Ph.D., of TIGR, and StevenSalzberg, Ph.D., of the University of Maryland, College Park, fullysequenced 209 strains of flu virus, determining the order of more than2.8 million nucleotide bases, the building blocks of DNA. Until now,the researchers note, most of the gene sequence information availableto scientists comprised only relatively short fragments of flu genesthat encode two of the virus' key surface proteins, hemagglutinin (H)and neuraminidase (N). In collaboration with David Lipman, M.D., andcolleagues at NCBI, NIAID will rapidly make this sequence informationpublicly available through GenBank�, an international, searchableonline database.
This was the first large-scale effort to sequence flu strains drawn atrandom from a geographically limited region: most strains came fromsamples submitted over five years to the New York State Department ofHealth. The sequenced strains were not pre-selected for virulence orother characteristics, giving researchers an unbiased view of flu virusevolution 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 geneticdiversity in the sequences. They learned, for example, that threegenetically distinct variants of the dominant H3N2 strain appeared overthe study period. In some seasons, these variants circulatedsimultaneously; New York residents were suffering from similar, butdistinct, versions of the virus.
With this new, highly detailed genomic information, the researchersfound out why the 2003-04 flu vaccine provided only partial protectionagainst that season's flu. During the 2002-03 season, distinctlydifferent versions of the H3N2 flu virus underwent genetic mixing. Theresulting strain emerged late in the season and became the predominantcause of flu the following year. However, the 2003-04 vaccine did nottarget the late-emerging version of H3N2 and so the vaccine providedless than optimal protection. In the future, say the researchers, rapidsequencing of flu strain variants could provide information needed tocraft vaccines precisely tailored against the most virulent strains.
"Through the Influenza Genome Sequencing Project, techniques have beenestablished to allow rapid sequencing of full genomes of influenzavirus. This project continues to move toward our goal of revealingcomplete genetic blueprints of thousands of known human and avianinfluenza viruses over the next several years," says Maria Y. Giovanni,Ph.D., who oversees NIAID's flu genome sequencing project.
For more information about the Influenza Genome Sequencing Project, visit the project Web site at http://www.niaid.nih.gov/dmid/genomes/mscs/influenza.htm. A press release issued at the launch of the genome project in November, 2004, is available at http://www3.niaid.nih.gov/news/newsreleases/2004/flugenome.htm. More information about the National Center for Biotechnology Information, part of NIH's National Library of Medicine, is at http://www.ncbi.nih.gov/.
NIAID is a component of the National Institutes of Health, an agency ofthe U.S. Department of Health and Human Services. NIAID supports basicand applied research to prevent, diagnose and treat infectious diseasessuch as HIV/AIDS and other sexually transmitted infections, influenza,tuberculosis, malaria and illness from potential agents ofbioterrorism. NIAID also supports research on transplantation andimmune-related illnesses, including autoimmune disorders, asthma andallergies.
Reference: E Ghedin et al. Large-scale sequencing of humaninfluenza reveals the dynamic nature of viral genome evolution. NaturePublished online Oct. 5, 2005. DOI: 10.1038/nature04239.
Materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Content may be edited for style and length.
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