Influenza - Clues To Influenza Evolution

Clues To Influenza Evolution

Study, Reported in Science, Identifies How Viral protein Mutations Lead to New Flu Strains

Irvine, Calif. -- Evolutionary studies of influenza have provided researchers at UC Irvine with information that could eventually result in the development of more effective flu vaccines.

professor Walter M. Fitch and assistant research biologist Robin M. Bush of UCI's Department of Ecology and Evolutionary Biology, working with researchers at the Centers for Disease Control and prevention, studied the evolution of a prevalent form of the influenza A virus during an 11-year period from 1986 to 1997. They discovered that viruses having mutations in certain parts of an important viral surface protein were more likely than other strains to spawn future influenza lineages. Human susceptibility to infection depends on immunity gained during past bouts of influenza; thus, new viral mutations are required for new epidemics to occur. Knowing which currently circulating mutant strains are more likely to have successful offspring potentially may help in vaccine strain selection. The researchers' findings appear in the Dec. 3 issue of Science magazine.

"Scientists haven't known how to predict which strain of influenza virus is going to be the progenitor of the strains that will cause future epidemics," Fitch said. "This is the first time that an evolutionary study has been used to identify which strains are most fit."

Fitch and his fellow researchers followed the evolutionary pattern of the influenza virus, one that involves a never-ending battle between the virus and its host. The human body fights the invading virus by making antibodies against it. The antibodies recognize the shape of proteins on the viral surface. previous infections only prepare the body to fight viruses with recognizable shapes. Thus, only those viruses that have undergone mutations that change their shape can cause disease. Over time, new strains of the virus continually emerge, spread and produce offspring lineages that undergo further mutations. This process is called antigenic drift. "The cycle goes on and on--new antibodies, new mutants," Fitch said.

The research into the virus' genetic data focused on the evolution of the hemagglutinin gene--the gene that codes for the major influenza surface protein. Fitch and fellow researchers constructed "family trees" for viral strains from 11 consecutive flu seasons. Each branch on the tree represents a new mutant strain of the virus. They found that the viral strains undergoing the greatest number of amino acid changes in specified positions of the hemagglutinin gene were most closely related to future influenza lineages in nine of the 11 flu seasons tested.

By studying the family trees of various flu strains, Fitch said, researchers can attempt to predict the evolution of an influenza virus and thus potentially aid in the development of more effective influenza vaccines. The Food and Drug Administration's Vaccines and Related Biological products Advisory Committee each year recommends an influenza vaccine for the coming flu season. A worldwide network of health organizations gathers influenza viruses from infected people, and this information is used to make recommendations about which flu strains are likely to circulate in the coming year.

Influenza viruses come in three types--A, B and C. While influenza C has very little public health impact, influenza A and B viruses are responsible for the epidemics of influenza that occur in the United States nearly every winter. Currently, two separate groups of influenza A viruses circulate worldwide along with type B influenza viruses. Influenza vaccines are designed to combat viruses in all three groups.

The research team is currently expanding its work to include all three groups of circulating influenza viruses, hoping that contrasting their evolutionary strategies may lend more insight into the evolution of influenza.

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