Scientists to Discuss Genetic Resistance to HIV
Reports that some individuals may be immune to infection with HIV have contributed significantly to the atmosphere of cautious optimism that currently surrounds AIDS research. In a symposium on Saturday, February 15, at the annual meeting of the American Association for the Advancement of Science (AAAS), leading researchers will explore these findings and discuss their implications for the development of strategies to prevent and treat HIV infection.
"In the last 10 years, much of AIDS research was focused on the genome of HIV and related viruses," explains symposium organizer Janet Young, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. "More recently, scientists have investigated the structures and functions of different cells involved in HIV pathogenesis. The knowledge gained has made it possible to begin asking questions about how some individuals seem able to resist HIV infection and disease."
The symposium, "Host Genes and Resistance to HIV Infection and AIDS," will open with a presentation on genetic susceptibility and resistance to human infectious diseases by Arno Motulsky, M.D., of the University of Washington in Seattle. "Although Dr. Motulsky is not an AIDS researcher, his expertise in host resistance to viruses will provide a useful introduction to this topic," says Dr. Young. The symposium will then feature presentations by current and former NIAID researchers and grantees.
Richard Kaslow, M.D., M.P.H., formerly of NIAID and now at the University of Alabama at Birmingham, will give a presentation titled "The Major Histocompatibility Complex and HIV Infection: Lessons and Applications." In analyses of individuals enrolled in the NIAID-funded Multicenter AIDS Cohort Study (MACS), Dr. Kaslow and other investigators have found that certain combinations of genes are associated with slow HIV disease progression while others correlate with rapid progression.
Francis Plummer, M.D., an NIAID-funded researcher at the University of Manitoba, Canada, will discuss "Mechanisms of Resistance to HIV-1 Infection in Continuously Exposed Prostitutes." Dr. Plummer and his colleagues have studied a small group of Kenyan prostitutes who remain HIV-negative despite many exposures to the virus. Although their blood cells can be infected with HIV in test tube experiments, these women share immune system genes that appear to be highly correlated with protection from infection. In ongoing studies, Dr. Plummer and his colleagues are examining potential mechanisms of HIV resistance in these women.
Edward Berger, Ph.D., chief of the Molecular Structure Section in NIAID's Laboratory of Viral Diseases, will discuss "HIV Fusion Cofactors: the Chemokine Receptor Connection." Dr. Berger's lab identified the first HIV co-receptor, a molecule that Dr. Berger and his colleagues dubbed "fusin." They showed that fusin must be present on the surface of CD4+ T cells in order for HIV to enter and infect these cells. Soon thereafter, Dr. Berger's group and others showed that other HIV strains use different co-receptors to gain entry into target cells. Many of these molecules ordinarily function as receptors for chemokines, proteins that help orchestrate immune responses.
Richard Koup, M.D., an NIAID grantee at the Aaron Diamond AIDS Research Center in New York, will present "Host Factors Involved in Resistance to HIV Infection." Dr. Koup and his colleagues reported that two HIV-negative men, both known to have had numerous high-risk exposures to the virus, possessed mutant forms of the gene encoding the chemokine receptor CCR-5. Previously, research groups led by Dr. Koup, Dr. Berger and others, independently discovered that CCR-5 is an HIV co-receptor, required by certain strains of the virus for entry into immune system cells.
Miles Cloyd, Ph.D., an NIAID-funded investigator at the University of Texas Medical Branch in Galveston, will discuss "Host Differential Genetic Susceptibility to HIV-1," and report evidence of a type of HIV resistance not related to mutations in HIV co-receptor molecules. In laboratory experiments, Dr. Cloyd and his colleagues infected blood cells from more than 50 healthy volunteers with HIV. In approximately 15 percent of the blood samples, they found that the virus entered target cells and copied RNA, its genetic material, into DNA as expected, but did not produce the RNA necessary to produce new virus. The new resistance mechanism, dubbed "post-entry restriction," is the first reported to arrest HIV reproduction after the virus has infected normal immune cells.
The symposium will take place Saturday, Feb. 15, 1997, from 2:30 p.m. to 5:30 p.m., Pacific Time, at the Washington State Convention and Trade Center in Seattle.
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.
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