Fauci: New Findings on Host Factors Illuminate AIDS Pathogenesis
A clearer picture is now emerging of how factors intrinsic to the HIV-infected individual influence the rate at which HIV replicates in the person's body and how rapidly the patient will develop AIDS, says Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID).
These so-called "host factors" include the specific immune response to the virus, non-specific factors and the individual's genetic makeup. Such factors are as important, or in some cases even more important, to the HIV disease process than the intrinsic virulence of the virus itself. Host factors together with viral factors determine the pathogenesis of HIV disease -- the complex events that lead to the destruction of an HIV-infected person's immune system.
Dr. Fauci, also the chief of the NIAID Laboratory of Immunoregulation, presents a synthesis of recent advances in the Dec. 12, 1996 issue of the journal Nature.
In the past few months we have witnessed a rapid and truly remarkable convergence of information from diverse areas of AIDS research," says Dr. Fauci. "In particular, scientists have made important new discoveries about the pathogenesis of HIV disease. These findings have created unprecedented opportunities for deciphering the HIV disease process, and provide the scientific basis for developing new treatment and vaccine strategies."
Taken together with other promising findings concerning the effectiveness of new combinations of anti-HIV drugs, recent insights into HIV pathogenesis have provided renewed optimism for people living with HIV disease as well as for the researchers working to understand and control this extraordinarily complex problem."
Among many important recent discoveries related to host factors in the pathogenesis of HIV disease, Dr. Fauci discusses the following:
- how the normal signaling molecules of a person's immune system (cytokines) regulate the level at which HIV replicates in the body, thereby influencing the rate of HIV disease progression. Some of these cytokines induce HIV replication and some of them suppress the virus; tipping the balance between these positive and negative forces can result in dramatic increases or decreases in HIV replication.
- how the activation of the immune system, by HIV itself as well as by other pathogens, allows HIV to replicate more efficiently.
- how different strains of HIV use recently discovered cell surface molecules, in addition to the well-known CD4 molecule, to bind to and enter their target cells. Intriguingly, these co-receptors are shared by the virus and certain of the body's own cytokines. Researchers speculate that certain cytokines suppress HIV infection by competitively occupying or downregulating the common receptor they share with HIV. Investigators now are exploring the feasibility of therapeutic strategies that might block these receptors with peptides, antibodies or pharmacologic means.
- new insights into the "tropism" or preference of different HIV strains for certain cells. Strains of HIV that infect macrophages and T cells are the main ones found in an HIV-infected person early in the course of disease; as time progresses, strains that replicate efficiently in T cells but not in macrophages appear, coincident with the decline of the immune system. This transition may be explained in part by the changing cytokine profiles and expression of co-receptors on cells in an HIV-infected person's body.
- how mutations in the human genes for HIV co-receptors may help explain why some individuals do not become infected with HIV despite repeated exposure, and why individuals who are HIV-infected may have very different rates of disease progression.
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 Public Health Service, U.S. Department of Health and Human Services.
Fauci AS. Host factors and the pathogenesis of HIV-induced disease. Nature 1996;384:529-534.
NIAID press releases, fact sheets and other materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov.