Overview

HIV disease is characterized by a gradual deterioration of immune function. Most notably, crucial immune cells called CD4+ T cells are disabled and killed during the typical course of infection. These cells, sometimes called "T-helper cells," play a central role in the immune response, signalling other cells in the immune system to perform their special functions.

A healthy, uninfected person usually has 800 to 1,200 CD4+ T cells per cubic millimeter (mm³) of blood. During HIV infection, the number of these cells in a person's blood progressively declines. When a person's CD4+ T cell count falls below 200/mm³, he or she becomes particularly vulnerable to the opportunistic infections and cancers that typify AIDS, the end stage of HIV disease. People with AIDS often suffer infections of the intestinal tract, lungs, brain, eyes and other organs, as well as debilitating weight loss, diarrhea, neurologic conditions and cancers such as Kaposi's sarcoma and lymphomas.

Most scientists think that HIV causes AIDS by directly killing CD4+ T cells and by triggering other events that weaken a person's immune function. For example, the network of signalling molecules that normally regulates a person's immune response is disrupted during HIV disease, impairing a person's ability to fight other infections. The HIV-mediated destruction of the lymph nodes and related immunologic organs also plays a major role in causing the immunosuppression seen in people with AIDS.

Scope of the HIV Epidemic

Although HIV was first identified in 1983, studies of previously stored blood samples indicate that the virus entered the U.S. population sometime in the late 1970s. In the United States, 513,486 cases of people with AIDS had been reported to the Centers for Disease Control and Prevention (CDC) as of Dec. 31, 1995. Among these individuals, 319,849 had died by the end of 1995. AIDS is now the leading killer of people aged 25 to 44 in this country.

Worldwide, an estimated 27.9 million people had become HIV-infected through mid-1996, and 7.7 million had developed AIDS, according to the World Health Organization (WHO). Various projections indicate that, by the year 2000, between 40 and 110 million people worldwide will be HIV-infected.

HIV is a Retrovirus

HIV belongs to a class of viruses called retroviruses, which have genes composed of ribonucleic acid (RNA) molecules. The genes of humans and most other organisms are made of a related molecule, deoxyribonucleic acid (DNA).

Like all viruses, HIV can replicate only inside cells, commandeering the cell's machinery to reproduce. However, only HIV and other retroviruses, once inside a cell, use an enzyme called reverse transcriptase to convert their RNA into DNA, which can be incorporated into the host cell's genes.

Slow viruses. HIV belongs to a subne activation and bursts of virus production, likely contribute to the progression of HIV disease.

NIAID Research on the Pathogenesis of AIDS

NIAID-supported scientists conduct HIV pathogenesis research in laboratories on the campus of the National Institutes of Health (NIH) in Bethesda, Md., at the Institute's Rocky Mountain Laboratories in Hamilton, Mont., and at universities and medical centers in the United States and abroad.

An NIAID-supported collaborative center of the World Health Organization, known as the NIH AIDS Research and Reference Reagent Program, provides AIDS-related research materials free to qualified researchers around the world.

In addition, the Institute convenes groups of investigators and advisory committees to exchange scientific information, clarify research priorities and bring research needs and opportunities to the attention of the scientific community.

The NIAID HIV/AIDS Research Agenda and NetMedicine Home Page on NIAID HIV/AIDS vaccine research, clinical trials for AIDS therapies and vaccines, and AIDS-related opportunistic infections are available from the NIAID Office of Communications. To receive free copies, call (301) 496-5717, Monday through Friday, 8:30 a.m. to 5:00 p.m. Eastern Time. These materials also are available via the NIAID home page on the Internet at http://www.niaid.nih.gov.

NIAID, a component of the National Institutes of Health, supports research on AIDS, tuberculosis and other infectious diseases, as well as allergies and immunology. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.

Glossary

Apoptosis: Cellular suicide, also known as programmed cell death. HIV may induce apoptosis in both infected and uninfected immune system cells.

B cells: White blood cells of the immune system that produce infection-fighting proteins called antibodies.

CD4+ T cells: White blood cells that orchestrate the immune response, signalling other cells in the immune system to perform their special functions. Also known as T helper cells, these cells are killed or disabled during HIV infection.

CD8+ T cells: White blood cells that kill cells infected with HIV or other viruses, or transformed by cancer. These cells also secrete soluble molecules that may suppress HIV without killing infected cells directly.

Cytokines: Proteins used for communication by cells of the immune system. Central to the normal regulation of the immune response.

Cytoplasm: The living matter within a cell.

Dendritic cells: Immune system cells with long, tentacle-like branches. Some of these are specialized cells at the mucosa that may bind to HIV following sexual exposure and carry the virus from the site of infection to the lymph nodes. See also follicular dendritic cells.

Enzyme: A protein that accelerates a specific chemical reaction without altering itself.

Follicular dendritic cells (FDCs): Cells found in the germinal centers (B cell areas) of lymphoid organs. FDCs have thread-like tentacles that form a web-like network to trap invaders and present them to B cells, which then make antibodies to attack the invaders.

Germinal centers: Structures within lymphoid tissues that contain FDCs and B cells, and in which immune responses are initiated.

gp41: Glycoprotein 41, a protein embedded in the outer envelope of HIV. Plays a key role in HIV's infection of CD4+ T cells by facilitating the fusion of the viral and cell membranes.

gp120: Glycoprotein 120, a protein that protrudes from the surface of HIV and binds to CD4+ T cells.

gp160: Glycoprotein 160, an HIV precursor protein that is cleaved by the HIV protease enzyme into gp41 and gp120.

Integrase: An HIV enzyme used by the virus to integrate its genetic material into the host cell's DNA.

Kaposi's sarcoma: A type of cancer characterized by abnormal growths of blood vessels that develop into purplish or brown lesions.

Killer T cells: See CD8+ T cells.

Lentivirus: "Slow" virus characterized by a long interval between infection and the onset of symptoms. HIV is a lentivirus as is the simian immunodeficiency virus (SIV), which infects nonhuman primates.

LTR: Long terminal repeat, the RNA sequences repeated at both ends of HIV's genetic material. These regulatory switches may help control viral transcription.

Lymphoid organs: Include tonsils, adenoids, lymph nodes, spleen and other tissues. Act as the body's filtering system, trapping invaders and presenting them to squadrons of immune cells that congregate there.

Macrophage: A large immune system cell that devours invading pathogens and other intruders. Stimulates other immune system cells by presenting them with small pieces of the invaders.

Monocyte: A circulating white blood cell that develops into a macrophage when it enters tissues.

Opportunistic infection: An illness caused by an organism that usually does not cause disease in a person with a normal immune system. People with advanced HIV infection suffer opportunistic infections of the lungs, brain, eyes and other organs.

Pathogenesis: The production or development of a disease. May be influenced by many factors, including the infecting microbe and the host's immune response.

Protease: An HIV enzyme used to cut large HIV proteins into smaller ones needed for the assembly of an infectious virus particle.

Provirus: DNA of a virus, such as HIV, that has been integrated into the genes of a host cell.

Retrovirus: HIV and other viruses that carry their genetic material in the form of RNA and that have the enzyme reverse transcriptase.

Reverse transcriptase: The enzyme produced by HIV and other retroviruses that allows them to synthesize DNA from their RNA.

Syncytia: Giant cells formed by the fusion of other cells.

Source:
Office of Communications
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892

Public Health Service
U.S. Department of Health and Human Services