Within the past year, a steady succession of studies have implicated molecules known as chemokine receptors as the long-sought co-factors that enable HIV to enter and infect immune system cells. Many scientists believe these findings could point the way toward more effective treatment and prevention strategies for HIV/AIDS. The rapid pace of discovery in this area supports their optimism. National Institute of Allergy and Infectious Diseases (NIAID) scientist Edward A. Berger, Ph.D, and otherleading chemokine receptor researchers, will discuss their latest findings in a symposium at the Fourth Conference on Retroviruses and Opportunistic Infections.
Dr. Berger's presentation, "HIV Entry and Tropism: When One Receptor Is Not Enough," will focus on new insights into the "tropism" or preference of different strains of HIV for certain cells of the human immune system. Strains of HIV that infect the immune system's macrophages and T cells are most often found in an HIV-infected individual early in the course of disease; as disease progresses, strains appear that replicate efficiently in T cells but not in macrophages. In a seminal study, Dr. Berger's team identified a molecule, later shown to be a chemokine receptor, that enables these late-stage HIV strains to enter and infect CD4+ T cells. Without this molecule, dubbed "fusin," HIV cannot infect these cells. Soon thereafter, Dr. Berger's group showed that the macrophage-tropic (early-stage) HIV strains use a different chemokine receptor, a molecule known as CCR5, to gain entry into target cells. Simultaneous with the Berger group's report, four other independent research groups published similar findings on CCR5's role in HIV entry. Scientists from each of these groups will take part in the symposium. They include:
Joseph G. Sodroski, M.D., Dana-Farber Cancer Institute, Boston: "Viral and Host Cell Factors in HIV Entry"
John P. Moore, Ph.D., Aaron Diamond AIDS Research Center, New York: "Secondary Receptors for Primary Viruses"
Robert W. Doms, Ph.D., University of Pennsylvania, Philadelphia: "Domains of Chemokine Receptors Required for HIV Entry"
Nathaniel R. Landau, Ph.D., Aaron Diamond AIDS Research Center, New York: "The Role of CCR-5 in HIV Entry and Susceptibility of Individuals to Infection"
Dr. Sodroski led a research team that showed that macrophage-tropic HIV strains can use the chemokine receptor CCR-3, in addition to CCR5, to infect target cells. More recently, he and his colleagues have reported new details about the biochemical interactions that occur between HIV, CCR5 and CD4.
In addition to providing independent confirmation of CCR5's role in infection by macrophage-tropic HIV strains, Dr. Moore and colleagues at the Aaron Diamond AIDS Research Center also have helped define the interactions between HIV and chemokine receptors. Both the Moore and Sodroski groups have demonstrated that HIV's gp120 protein interacts directly with CCR5 and that binding is greatly enhanced when CD4 molecules also are present.
Researchers led by Dr. Doms showed that macrophage-tropic HIV strains use not only CCR5 or CCR3 to enter and infect cells, but also the chemokine receptor CCR-2b. The Doms group subsequently collaborated with a Belgian research team to report that individuals who have resisted HIV infection despite multiple high-risk exposures to the virus have a defect in the gene that encodes the CCR5 molecule, a finding also reported by Dr. Landau and his colleagues.
Scientists are optimistic that these findings and ongoing studies will lead to the development of agents to block chemokine receptors or mimic the protective effect of the mutant chemokine receptor gene. This research may also lead to the development of better animal models of HIV infection, essential tools for evaluating new drugs and vaccines.
The symposium, titled "HIV Entry Co-factors: the Chemokine Receptor Connection," will take place Thursday, January 23, 1997 from 2:00 p.m. to 4:00 p.m. at the Sheraton Washington Hotel in Washington, D.C.
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.