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Global Health Matters

July - August, 2007  |  Volume 6, Issue 4

Spread of Drug-Resistant Influenza Viruses Studied

The NIH/Fogarty research team
was led by NIAID senior scientist
Dr. Lone Simonsen

Over the last few years, human influenza viruses resistant to antiviral drugs have spread worldwide. A recent analysis of influenza genomes led by the National Institute of Allergy and Infectious Diseases (NIAID) and Fogarty, suggests this surge in resistance has not occurred in response to selection imposed by antiviral drugs. Rather, the mutation that causes resistance appears to be associated with fitness-enhancing changes elsewhere in the genome.

The study—published in Molecular Biology and Evolution—reports that in many areas of the world, the predominant strain of human influenza virus (A/H3N2) has become rapidly resistant to a major class of drugs called adamantanes, a set of commonly-used, first generation antivirals. In the U.S., China and Japan more than 90 percent of the viruses circulating in the 2005-2006 influenza season were resistant, compared with fewer than five percent before 2003.

In almost all cases, adamantane resistance arises from a single amino acid change in a membrane protein. The research team, led by NIAID senior scientist Dr. Lone Simonsen,
examined the genomes of viruses isolated from New Zealand, Australia, Japan
and the U.S. between 2004 and 2006.

All adamantane-resistant viruses examined belonged to a distinct lineage (the N-lineage) that first circulated in the Southern Hemisphere and Asia in 2005, then spread to the northern hemisphere during 2006. This N-lineage appears to have arisen from reassortment between two other influenza A/H3N2 lineages. There is no doubt that the selective pressure generated from drugs still plays a significant role in the emergence of drug resistance, the study says. However, the adamantane case is a strong reminder that other forces are also at play.

Those factors will have to be accounted for in developing disease-management strategies, says Dr. Edwin D. Kilbourne, professor emeritus of microbiology and immunology at New York Medical College. "This paper has great practical implications for planning for future pandemics, if they occur," he says.

Fogarty’s Division of International Epidemiology and Population Studies Director Dr. Mark A. Miller agrees. He adds that the work is also an important example of how useful it can be to share influenza data. "Virologists the world over have had a lot of difficulty sharing viral genomes," he notes. "This publication illustrates the power of a multinational collaboration where viruses and their whole genomes are shared to advance public health."

The study was a joint effort of NIAID and Fogarty; the Center for Infectious Disease Dynamics, Department of Biology, Pennsylvania State University; the Department of Ecology and Evolutionary Biology, Princeton University; the Canterbury Health Laboratories, New Zealand; the Los Alamos National Laboratory; Department of Microbiology, Aichi Prefectural Institute of Public Health, Japan and the Department of Zoology, University of Cambridge, U.K.

The Genesis and Spread of Reassortant Human Influenza A/H3N2 Viruses Conferring Adamantane Resistance. Simonsen L, Viboud C, Bryan T, Grenfell BT, Dushoff J, Jennings L, Smit M, Macken C, Hata M, Gog J, Miller MA, Holmes EC. Molecular Biology and Evolution, doi:10.1093/molbev/msm103.