Scientists map flu's chemical key

Scientists from Baylor College of Medicine (BCM) and Rice University have developed a three-dimensional, molecular map that could yield clues about the genetic mutations that will allow bird flu to spread among humans.

The research, which appears this week in the Proceedings of the National Academy of Science (PNAS) Online Early Edition, was conducted on a strain of the influenza B virus initially isolated from Hong Kong. Unlike strains of influenza A -- which include bird flu, swine flu and others -- influenza B affects only humans.

"The big question is, 'What would it take for the bird flu to change and start killing us"'" said research co-author Jianpeng Ma, a structural biologist who holds joint appointments at both BCM and Rice. "Since flu B is a distant relative of flu A, the fewer common features among them would allow identifying the critical parts required for infecting humans."

The research is based on a more than six years of painstaking experiments by lead author Qinghua Wang, assistant professor of biochemistry and molecular biology at BCM. The experiments focused on a protein called hemagglutinin (HA), the chemical key that allows flu viruses to attach to target cells and infect them with viral DNA. There are 16 HA proteins, but only flu B and H1, H2 and H3 of flu A are found in human-transmissible strains. Scientists know H5, the HA key used by bird flu, is very similar to the chemical keys used by human strains of flu A. Like all proteins, the HA keys consist of a precise sequence of amino acids.

"In terms of sequence, there is only a 25 percent overlap between HA proteins for type A and type B," Ma said. "But in terms of function, the two are remarkably similar.

Wang said, "It would be better if there were more differences. The similarities suggest that only minor mutations are needed for bird flu to become transmissible to human."

Scientists know the precise 3D structure of several HA keys for flu A, but Wang and Ma's work represents the first mapping of an HA key for flu B. Currently, Ma and Wang are working out the precise molecular mutations that will be required for bird flu's HA to change into a human transmissible form.

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