|Genomes of More than 200 Human Flu Strains Reveal a Dynamic
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.
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/.
News releases, fact sheets and other NIAID-related materials are available
on the NIAID Web site at http://www.niaid.nih.gov.
NIAID is a component of the National Institutes of Health, an agency of
the U.S. Department of Health and Human Services. NIAID supports basic and
applied research to prevent, diagnose and treat infectious diseases such as
HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis,
malaria and illness from potential agents of bioterrorism. NIAID also supports
research on transplantation and immune-related illnesses, including autoimmune
disorders, asthma and allergies.
The National Institutes of Health (NIH) — The Nation's Medical Research
Agency — includes 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary Federal
agency for conducting and supporting basic, clinical, and translational medical
research, and it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.