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Most flu researchers agree that currently the most worrisome strain of avian influenza is H5N1, a highly lethal strain that has been infecting poultry and people in Southeast Asia. But what makes one H5 strain more deadly than another?
David Wentworth, Ph.D., a NIAID-supported researcher with Wadsworth Center, the state of New York’s health laboratory, wonders if a clue may be surreptitiously lurking within the H5 gene.
Dr. Wentworth is investigating a suspicious segment of RNA—the genetic material of flu virus—that he first discovered while doing graduate work with Virginia Hinshaw, Ph.D., at the University of Wisconsin-Madison. The segment—called a promoter because it is able to turn a gene on or off—was discovered on the HA gene of an H5N9 virus that was killing turkeys in Ontario, Canada. But unlike normal promoters that precede the genes they direct, this promoter is hidden within the gene. Dr. Wentworth wants to find out if the segment is doing more than just occupying space.
“We’re curious whether this segment might lead to something—a new protein, perhaps,” says Dr. Wentworth. “If so, we’d like to know what the protein’s function is. Does it determine virulence, or does it have a different function altogether?”
Using reverse genetics, Dr. Wentworth is recreating the Ontario strain and comparing what happens when the promoter is fully functional with what happens when mutations are introduced to disable the promoter. When the promoter is intact, the H5 strain has been found to be highly lethal in the laboratory, killing 100 percent of infected chickens within 72 hours. His hope is that what he learns could be helpful in the event the H5N1 virus become a pandemic.
“The goal of this study is to understand at a molecular level the mechanisms that influenza viruses employ to cause disease,” he says. “If we can find what makes some strains so virulent, then perhaps we can address those key features through drugs and other antiviral approaches.”
In 2011, Dr. Wentworth and colleagues published research in the Journal of Virology about a way to use reverse genetics to better understand the Canadian strain of avian flu.
B Zhou et al. Reverse genetics plasmid for cloning unstable influenza A virus gene segments. Journal of Virology. DOI: 10.1016/j.jviromet.2011.01.021 (2011).
Last Updated March 12, 2013
Last Reviewed March 12, 2013