Peter C. Doherty, PhD, Richard J. Webby, PhD, Paul Thomas

    H5N1 threat puts human flu back in spotlight

    Review article by St. Jude researchers notes renewed interest in studying influenza A viruses, which could lead to better drugs and vaccines for both avian and human influenza

    The emergence of the bird flu virus H5N1 that is currently devastating chicken flocks in many countries and threatening to unleash a worldwide epidemic among humans has triggered a renewed interest among scientists in studying influenza A viruses, according to investigators at St. Jude Children’s Research Hospital.

    “Over the years, influenza A viruses have been one of the most important models for studying how the immune system responds to viral infections,” said Peter Doherty, Ph.D. a member of the Department of Immunology at St. Jude and co-recipient of the 1996 Nobel Prize for Medicine. Doherty is the senior author of a review article that appears in the May issue of Nature Immunology. “Further study of this virus and the immune response to it will no doubt help us prepare for this latest threat.”

    The first way the immune system responds to influenza A viruses is by stimulating B lymphocytes to develop into antibody-forming plasma cells, according to Doherty. “If we have the “right” antibodies in our blood as a consequence of being vaccinated we are completely protected,” he said. However, the HA and NA proteins on the surface of these viruses continually mutate, keeping a step ahead of the “posse” of antibodies that seek to bring them down.

    On the other hand, the CD8+ “killer” T lymphocytes, which attack and kill cells infected by the virus, take longer to respond, and the virus still replicates extensively before these cells do their job. Even before people realize they’re infected, they can spread the virus.

    According to the authors, the “Holy Grail” of influenza vaccines would be one that would target “universal” antigens (targets) that appear on all flu viruses and that don’t readily mutate.
    The other authors of the paper are Paul Thomas (Immunology, St. Jude) Richard Webby (Infectious Diseases, St. Jude) and Stephen Turner (University of Melbourne, Australia).

    This work was supported in part by the National Institutes of Health, the Australian National Health and Medical Research Council, Science Technology, Innovation funds from the State of Victoria, Australia, and ALSAC.

    Last update: June 2006