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Algorithm Helps Identify Viral Strains, Mutations

Influenza ultrastructure illustration (Dan Higgins, CDC)

Influenza ultrastructure illustration (Dan Higgins, CDC)

Researchers in Israel and the U.S. have developed computational methods to analyze the composition of proteins that control a virus’s ability to attach to host cells and produce more virus. The unique position of amino acids in those proteins acts as a signature for the virus, and identifying that signature can help pinpoint the virus’s different mutations and strains.

Nir Ben-Tal of Tel Aviv University’s Department of Biochemistry and Molecular Biology, with colleagues from Tel Aviv, Fred Hutchinson Cancer Research Center in Seattle, and St. Jude Children’s Research Hospital in Memphis focused on the 2009 strain of the H1N1 flu virus. Their findings appear this month the Proceedings of the National Academy of Sciences.

To determine the spread of the 2009 H1N1 flu, Ben-Tal and colleagues analyzed the hemagglutinin protein, which controls the virus’s ability to fuse to a host cell in the body and transfer the genome which contains the information needed to make more virus. With many viruses, the body’s immune system is eventually able to recognize a virus’s hemagglutinin, which triggers its reaction to fight against the virus.

Using a statistical learning algorithm, the researchers compared amino acid positions in the pandemic 2009 strain of H1N1 against the common seasonal H1N1 flu. The team discovered that major sequence changes that had occurred in the 2009 H1N1 virus, altering antigenic sites and compromising the immune system’s ability to recognize and react to the virus.

The researchers’ method shows that mutations in specific positions of the H1N1 virus’ amino acids, such as antigenic receptor sites, may explain how the new strain successfully spread throughout the population in 2009. These alterations allowed the strain to evade both existing vaccines and the immune system’s defenses.

Using the algorithm, Ben-Tal’s team found that that the main differences between the pandemic strain and the common seasonal H1N1 strain are in some 10 amino acid positions. Experiments later conducted at St. Jude Children’s Research Hospital confirmed some of the theoretical predictions.

Because of their ability to mutate quickly, viruses can spread widely and rapidly, and general vaccines can be inefficient tools to control their spread. In the future, says Ben-Tal, a refined version of the algorithm may be used to generically compare various strains of viruses, and help predict how a strain will morph and if a pandemic could strike.

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