A National Institute of Allergy and Infectious Diseases (NIAID) intramural research team is co-winner of this year's prestigious American Association for the Advancement of Science (AAAS)-Newcomb Cleveland Prize, awarded to the authors of the best paper published in Science, as judged by the journal's editors. The award-winning paper by NIAID's Edward A. Berger, Ph.D., and his Laboratory of Viral Diseases (LVD) colleagues, Yu Feng, Ph.D., Christopher C. Broder, Ph.D., and Paul E. Kennedy, B.S., described crucial new information about how the human immunodeficiency virus (HIV) infects immune system cells.
Since the early years of the AIDS epidemic, scientists have recognized that HIV attacks white blood cells known as T lymphocytes that display a molecule known as CD4 on their surface. Studies have shown, however, that CD4 alone is insufficient to allow the virus to infect these cells; another molecule is also required. In their study, Dr. Berger and his co-authors identified that second molecule and showed that it enables certain strains of HIV to fuse with and enter CD4 positive (CD4+) T cells. The molecule, which the Berger team dubbed "fusin," is a receptor for immune system proteins called chemokines. The researchers showed that certain non-human cells that normally are resistant to HIV become susceptible to infection with the virus after the DNA encoding CD4 and fusin are introduced. They also found that antibodies to fusin block HIV entry into human cells that ordinarily would become infected.
The study by Dr. Berger and his colleagues is extremely important and well-deserving of the AAAS-Newcomb Cleveland Prize," says NIAID Director Anthony S. Fauci, M.D. "The recent discoveries made by Dr. Berger and other scientists have created unprecedented opportunities for deciphering the HIV disease process, and provide the scientific basis for developing new treatment and vaccine strategies."
Soon after the Berger team's seminal finding was published, they and other researchers reported the discovery of a different chemokine receptor used by other strains of HIV to enter and infect CD4+ cells. Scientists conducted genetic studies of a group of individuals who have remained HIV-negative despite multiple high-risk exposures to the virus, and they found a defect in the gene that encodes this chemokine receptor. These findings suggest that HIV infection might be prevented or treated with vaccines or drugs that block the chemokine receptors.
Dr. Berger adds that applying the chemokine receptor findings to the development of small animal models of HIV infection would be a valuable tool in the search for anti-HIV drugs and vaccines.
Transgenic mice and rabbits expressing human CD4 molecules have been developed, but they support HIV replication poorly," says Dr. Berger. "Transgenic animals expressing both CD4 and chemokine receptors may be more useful."
Dr. Berger has been at NIAID since 1987 and has been chief of LVD's Molecular Structure Section since 1995. He and his NIAID colleagues share the 1995-96 Newcomb Cleveland Prize with physicists from the University of Colorado and the National Institute of Standards and Technology. Their report of the first creation of a Bose-Einstein condensate, a state of matter predicted by Albert Einstein in 1924, may advance the implementation of atomic lasers and may help scientists gain a better understanding of superconductivity and quantum mechanics.
Established in 1923, the AAAS-Newcomb Cleveland Prize is the AAAS's oldest award. Awardees receive $5,000 and a bronze medal. The Prizes will be presented next month at the AAAS annual meeting in Seattle, Wash.
NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as HIV disease and other sexually transmitted diseases, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.
NIAID press releases, fact sheets and other materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov.
Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry co-factor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996;272:872-7. (May 10, 1996).