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H1N1 influenza adopted novel strategy to move from birds to humans
Date:12/8/2009

re efficient in human cells.

"This is an extremely rare mutation and a rare combination, which suggests that there may be other ways that haven't emerged yet that these viruses are going to continue to evolve," said Jennifer Doudna, UC Berkeley professor of molecular and cell biology and an investigator in the Howard Hughes Medical Institute.

"As mechanistic biologists, we are hoping that by understanding how the virus works at the molecular level, we will be able to predict with more accuracy how it will evolve."

She suggested that those monitoring influenza outbreaks around the world in search of new variants be on the lookout for this recombination of polymerase subunits, which could herald an uptick in swine flu virulence. The findings also could help scientists develop better antiviral treatments, Mehle and Doudna said.

"The more we can understand the biochemistry and the particular structure of these polymerase complexes, the better we can make rational decisions about drug development," Mehle said.

H1N1, which appeared on the scene earlier this year, was dubbed swine flu because it emerged from pigs, in which human, bird and pig influenza viruses mixed, swapped genes and gave rise to a variant that could infect human cells and reproduce.

While mutations in the surface protein hemagglutinin indicated by the H in H1N1 are key to allowing the virus to enter human cells, mutations in the polymerase enzyme are key to the virus's ability to replicate inside human cells. All previous flu strains that entered and were transmitted in humans had a single mutation in the second subunit of the bird polymerase gene, which apparently allowed the enzyme to operate in human cells.

Last year, Mehle and Doudna showed that human cells apparently prevent the three subunits of bird virus polymerases from assembling into a functioning enzyme. A single amino acid switch at position 627 on the second subunit of
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Contact: Robert Sanders
rsanders@berkeley.edu
510-643-6998
University of California - Berkeley
Source:Eurekalert

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