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Influenza A virus (IAV), the type of flu that causes most seasonal and pandemic outbreaks, has been studied extensively in animal models and tissue cultures. However, the way that IAV moves through the human respiratory system and infects its cells is not well understood. A major barrier to performing the in vivo studies that could provide this information was that scientists were unable to express in the virus a reporter gene that could be used to track its movement through the body.
But recently, NIAID-supported researchers at the Mount Sinai School of Medicine found a way to do just that. Led by Adolfo García-Sastre, Ph.D., the investigators created a recombinant IAV strain carrying a green fluorescent protein (GFP) reporter gene in the NS segment. When tested in mice, the new NS1-GFP virus was found to replicate efficiently and have pathogenic effects, although it was less pathogenic than the wild type virus. The researchers also traced infection progression in mice using imaging and cytometry. They then tested the effects of two IAV inhibitors, oseltamivir and amantadine, on these movements, and found differences between the inhibitors in the types of cells affected and the magnitude of infection reduction.
This study sets the stage for future research. “By visualizing the in vivo targets of IAV infection and the dynamics of infection progression,” the authors write, “we are likely to gain a better understanding of IAV pathogenesis.” The NS1-GFP strain could also be used in future in vivo studies to answer new research questions.
Manicassamy B, Manicassamy S, Belicha-Villanueva A, Pisanelli G, Pulendran B, García-Sastre A. Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus. Proc Natl Acad Sci. 2010 Jun 7; early online edition.
Last Updated June 28, 2010
Last Reviewed June 24, 2010