H1N1 Flu Virus Used New Biochemical Trick To To Spread Efficiently In Humans

Main Category: Swine Flu
Also Included In: Infectious Diseases / Bacteria / Viruses
Article Date: 05 Aug 2010 - 14:00 PDT


The recent pandemic-causing H1N1 flu virus used a new biochemical trick to spread efficiently in humans, according to an international team of scientists. The details, published August 5 in the open-access journal PLoS Pathogens, expand the repertoire of known factors flu viruses can use to hijack a host cell and amplify infection in mammals, including humans. The discovery not only yields new insight into the subtle biology of flu, but also reveals another genetic marker public health officials can use to presage pandemics.

The H1N1 flu virus, a combination of four different avian and swine flu viruses, caused a worldwide epidemic in 2009 and 2010, sickening as many as 34 million Americans and causing up to an estimated 6,000 deaths in the United States alone, according to the CDC.

Typically, the presence of two amino acids -- lysine and asparagines -- in specific sites on a key avian virus protein are required for a flu virus to make the jump from an animal host and replicate efficiently in human cells. The H1N1 virus lacked both of these amino acid building blocks, posing a puzzle for scientists.

The new study, conducted in mice, found that the lysine amino acid resides in a completely different location on the protein and is responsible for the H1N1 virus' ability to adapt to and co-opt human cells. Moreover, this misplaced amino acid substantially increases the lethality of an avian H5N1 virus.

"This pandemic H1N1 has this mutation and is why it can replicate so well in humans," says co-author Yoshihiro Kawaoka of the University of Wisconsin-Madison's School of Veterinary Medicine and the University of Tokyo. "This gives us another marker to help predict the possibility of future flu pandemics."

The new study also includes critical data for the three-dimensional structure of the H1N1 protein known as PB2, which originated from an avian virus. The structural data, says Kawaoka, provides essential insight into how the virus interacts with the host cell, and could help provide a basis for antiviral agents that could be used to thwart a future flu virus that uses the same amino acid trick to infect human cells.

According to co-author Bart L. Staker of Emerald BioStructures, Inc., the structural data also reveals changes in the surface shape of the avian virus protein in H1N1, which could, in turn, be responsible for thwarting factors in the human cell that would otherwise inhibit infection.

"Biological and Structural Characterization of a Host-Adapting Amino Acid in Influenza Virus"
Yamada S, Hatta M, Staker BL, Watanabe S, Imai M, et al. (2010)
PLoS Pathog 6(8): e1001034. doi:10.1371/journal.ppat.1001034

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