How HIV Causes AIDS 

An important focus of the National Institute of Allergy and Infectious Diseases (NIAID) is research devoted to the pathogenesis of human immunodeficiency virus (HIV) disease ? the complex mechanisms that result in the destruction of the immune system of an HIV-infected person. A detailed understanding of HIV and how it establishes infection and causes the acquired immunodeficiency syndrome (AIDS) is crucial to identifying and developing effective drugs and vaccines to fight HIV and AIDS. This fact sheet summarizes what scientists are learning about this process and provides a brief glossary of terms.

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 or interfering with their normal function, 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.

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, 612,078 cases of AIDS, and 379,258 deaths among people with AIDS had been reported to the Centers for Disease Control and Prevention (CDC) as of June 30, 1997. AIDS is now the second leading killer of people aged 25 to 44 in this country. Despite an overall stabilization in the number of new AIDS cases in this country, the epidemic continues to accelerate in certain segments of the population, notably among women and injection drug users.

Worldwide, an estimated 30.6 million people were living with HIV/AIDS as of December 1997, a figure that is projected to reach 40 million by the year 2000. More than 75 percent of all adult HIV infections have resulted from heterosexual intercourse. Through 1997, cumulative HIV/AIDS-associated deaths worldwide numbered approximately 11.7 million ? 9 million adults and 2.7 million children. 

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 subgroup of retroviruses known as lentiviruses, or "slow" viruses. The course of infection with these viruses is characterized by a long interval between initial infection and the onset of serious symptoms. 

Other lentiviruses infect nonhuman species. For example, the feline immunodeficiency virus (FIV) infects cats and the simian immunodeficiency virus (SIV) infects monkeys and other nonhuman primates. Like HIV in humans, these animal viruses primarily infect immune system cells, often causing immunodeficiency and AIDS-like symptoms. These viruses and their hosts have provided researchers with useful, albeit imperfect, models of the HIV disease process in people.

Organization of the HIV-1 Virion

Structure of HIV

The viral envelope. HIV has a diameter of 1/10,000 of a millimeter and is spherical in shape. The outer coat of the virus, known as the viral envelope, is composed of two layers of fatty molecules called lipids, taken from the membrane of a human cell when a newly formed virus particle buds from the cell. 

Embedded in the viral envelope are proteins from the host cell, as well as 72 copies (on average) of a complex HIV protein that protrudes from the envelope surface. This protein, known as Env, consists of a cap made of three or four molecules called glycoprotein (gp)120, and a stem consisting of three or four gp41 molecules that anchor the structure in the viral envelope. Much of the research to develop a vaccine against HIV has focused on these envelope proteins. 

The viral core. Within the envelope of a mature HIV particle is a bullet-shaped core or capsid, made of 2000 copies of another viral protein, p24. The capsid surrounds two single strands of HIV RNA, each of which has a copy of the virus's nine genes. Three of these, gag, pol and env, contain information needed to make structural proteins for new virus particles. The env gene, for example, codes for a protein called gp160 that is broken down by a viral enzyme to form gp120 and gp41, the components of Env.

Three regulatory genes, tat, rev and nef, and three auxiliary genes, vif, vpr and vpu, contain information necessary for the production of proteins that control the ability of HIV to infect a cell, produce new copies of virus or cause disease. The protein encoded by nef, for instance, appears necessary for the virus to replicate efficiently, and the vpu-encoded protein influences the release of new virus particles from infected cells.

The ends of each strand of HIV RNA contain an RNA sequence called the long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell.

The core of HIV also includes a protein called p7, the HIV nucleocapsid protein; and three enzymes that carry out later steps in the virus's life cycle: reverse transcriptase, integrase and protease. Another HIV protein called p17, or the HIV matrix protein, lies between the viral core and the viral envelope.
 

Life Cyle of HIV
Steps in Viral Replication Attachment/Entry Reverse Transcription and DNA Synthesis Transport to Nucleus Integration Viral Transcription Viral Protein Synthesis Assembly of Virus Release of Virus Maturation

Entry of HIV into cells. Infection typically begins when an HIV particle, which contains two copies of the HIV RNA, encounters a cell with a surface molecule called cluster designation 4 (CD4). Cells with this molecule are known as CD4 positive (CD4+) cells. 

One or more of the virus's gp120 molecules binds tightly to CD4 molecule(s) on the cell's surface. The membranes of the virus and the cell fuse, a process that probably involves the envelope of HIV and a second "coreceptor" molecule on the cell surface. Following fusion, the virus's RNA, proteins and enzymes are released into the cell. 

Recent studies by NIAID intramural and extramural researchers have identified multiple coreceptors for different types of HIV strains; these coreceptors are promising targets for new anti-HIV drugs. In the early stage of HIV disease, most people harbor viruses that use, in addition to CD4, a receptor called CCR5 to enter their target cells. With disease progression, the spectrum of coreceptor usage expands to include others, notably a molecule called CXCR4.

Although CD4+ T cells appear to be HIV's main target, other immune system cells with CD4 molecules on their surfaces are infected as well. Among these are long-lived cells called monocytes and macrophages, which apparently can harbor large quantities of the virus without being killed, thus acting as reservoirs of HIV. CD4+ T cells also serve as important reservoirs of HIV: a small proportion of these cells harbor HIV in a stable, inactive form. Normal immune processes may activate these cells, resulting in the production of new HIV virions.

Cell-to-cell spread of HIV also can occur through the CD4-mediated fusion of an infected cell with an uninfected cell.

Reverse transcription. In the cytoplasm of the cell, HIV reverse transcriptase converts viral RNA into DNA, the nucleic acid form in which the cell carries its genes. Seven of the 11 antiviral drugs approved in the United States for the treatment of people with HIV infection ? AZT, ddC, ddI, d4T, 3TC nevirapine and delavirdine ? work by interfering with this stage of the viral life cycle.

Integration. The newly made HIV DNA moves to the cell's nucleus, where it is spliced into the host's DNA with the help of HIV integrase. Once incorporated into the cell's genes, HIV DNA is called a "provirus." Integrase is an important target for the development of new drugs.

Transcription. For a provirus to produce new viruses, RNA copies must be made that can be read by the host cell's protein-making machinery. These copies are called messenger RNA (mRNA), and production of mRNA is called transcription, a process that involves the host cell's own enzymes. Viral genes in concert with the cellular machinery control this process: the tat gene, for example, encodes a protein that accelerates transcription. 

Cytokines, proteins involved in the normal regulation of the immune response, also may regulate transcription. Molecules such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, secreted in elevated levels by the cells of HIV-infected people, may help to activate HIV proviruses. Other infections, by organisms such as Mycobacterium tuberculosis, may also enhance transcription.

Translation. After HIV mRNA is processed in the cell's nucleus, it is transported to the cytoplasm. HIV proteins are critical to this process: for example, a protein encoded by the rev gene allows mRNA encoding HIV structural proteins to be transferred from the nucleus to the cytoplasm. Without the rev protein, structural proteins are not made.

In the cytoplasm, the virus co-opts the cell's protein-making machinery ? including structures called ribosomes ? to make long chains of viral proteins and enzymes, using HIV mRNA as a template. This process is called translation.

Assembly and budding. Newly made HIV core proteins, enzymes and RNA gather just inside the cell's membrane, while the viral envelope proteins aggregate within the membrane. An immature viral particle forms and pinches off from the cell, acquiring an envelope that includes both cellular and HIV proteins from the cell membrane. During this part of the viral life cycle, the core of the virus is immature and the virus is not yet infectious. The long chains of proteins and enzymes that make up the immature viral core are now cleaved into smaller pieces by a viral enzyme called protease. This step results in infectious viral particles. 

Drugs called protease inhibitors interfere with this step of the viral life cycle. Four such drugs ? saquinavir, ritonavir, indinavir and nelfinavir ? have been approved for marketing in the United States.

Among adults, HIV is spread most commonly during sexual intercourse with an infected partner. During sex, the virus can enter the body through the mucosal linings of the vagina, vulva, penis, rectum or, rarely, via the mouth. The likelihood of transmission is increased by factors that may damage these linings, especially other sexually transmitted diseases that cause ulcers or inflammation. 

Research suggests that immune system cells called dendritic cells, which reside in the mucosa, may begin the infection process after sexual exposure by binding to and carrying the virus from the site of infection to the lymph nodes where other immune system cells become infected.

HIV also can be transmitted by contact with infected blood, most often by the sharing of drug needles or syringes contaminated with minute quantities of blood containing the virus. The risk of acquiring HIV from blood transfusions is now extremely small in the United States, as all blood products in this country are screened routinely for evidence of the virus. 

Almost all HIV-infected children acquire the virus from their mothers before or during birth. In the United States, approximately 25 percent of pregnant HIV-infected women not receiving antiretroviral therapy have passed on the virus to their babies. NIAID-sponsored researchers have shown that a specific regimen of the drug zidovudine (AZT) can reduce the risk of transmission of HIV from mother to baby by two-thirds. Research using combinations of approved anti-HIV drugs is underway to determine if the transmission rate can be further reduced.

The virus also may be transmitted from a nursing HIV-infected mother to her infant.

Once it enters the body, HIV infects a large number of CD4+ cells and replicates rapidly. During this acute or primary phase of infection, the blood contains many viral particles that spread throughout the body, seeding various organs, particularly the lymphoid organs. Lymphoid organs include the lymph nodes, spleen, tonsils and adenoids.

During the acute phase of infection, the number of CD4+ T cells in the bloodstream decreases by 20 to 40 percent. Scientists do not yet know whether these cells are killed by HIV or if they leave the blood and go to the lymphoid organs in preparation to mount an immune response.

Two to four weeks after exposure to the virus, up to 70 percent of HIV-infected persons suffer flu-like symptoms related to the acute infection. The patient's immune system fights back with killer T cells (CD8+ T cells) and B-cell-produced antibodies, which dramatically reduce HIV levels. A patient's CD4+ T cell count may rebound to 80 to 90 percent of its original level. A person then may remain free of HIV-related symptoms for years despite continuous replication of HIV in the lymphoid organs seeded during the acute phase of infection.

One reason HIV is unique is that despite the body's aggressive immune responses, which are sufficient to clear most viral infections, some HIV invariably escapes. This is due in large part to the high rate of mutations that occur during the process of HIV replication. Even when the virus does not avoid the immune system by mutating , the body’s best soldiers in the fight against HIV ? certain subsets of killer T cells ? may multiply so rapidly following initial infection that they become exhausted and disappear, allowing HIV to escape and continue replication. 

In addition, early in the course of HIV infection, patients may lose HIV-specific CD4+ T cell responses that normally slow the replication of viruses. Such responses include the secretion of interferons and other antiviral factors, and the orchestration of CD8+ T cells.

Among patients enrolled in large epidemiologic studies in western countries, the median time from infection with HIV to the development of AIDS-related symptoms has been approximately 10 to 12 years. However, researchers have observed a wide variation in disease progression. Approximately 10 percent of HIV-infected people in these studies have progressed to AIDS within the first two to three years following infection, while up to 5 percent of individuals in the studies have stable CD4+ T cell counts and no symptoms even after 12 or more years.

Factors such as age or genetic differences among individuals, the level of virulence of an individual strain of virus, and co-infection with other microbes may influence the rate and severity of disease progression. Drugs that fight the infections associated with AIDS have improved and prolonged the lives of HIV-infected people by preventing or treating conditions such as Pneumocystis carinii pneumonia.

HIV co-receptors and disease progression. Recent research has shown that most infecting strains of HIV use a co-receptor molecule called CCR5, in addition to the CD4 molecule, to enter certain of its target cells. HIV-infected people with a specific mutation in one of their two copies of the gene for this receptor generally have a slower disease course than people with two normal copies of the gene. Rare individuals with two mutant copies of the CCR5 gene appear ? in most cases ? to be completely protected from HIV infection. Mutations in the gene for other HIV co-receptors also may influence the rate of disease progression.

Viral burden predicts disease progression. Numerous studies show that people with high levels of HIV in their bloodstream are more likely to develop new AIDS-related symptoms or die than individuals with lower levels of virus. For instance, in the Multicenter AIDS Cohort Study (MACS), NIAID-supported investigators demonstrated that the level of HIV in an individual's plasma soon after infection ? the so-called viral "set point" ? is highly predictive of the rate of disease progression; that is, patients with high levels of virus are much more likely to get sicker, faster, than those with low levels of virus. The MACS and other studies have provided the rationale for providing aggressive antiretroviral therapy to HIV-infected people, as well as for routinely using newly available blood tests to measure viral load when initiating, monitoring and modifying anti-HIV therapy. 

New anti-HIV drug combinations ? which generally include a protease inhibitor taken with two reverse transcriptase inhibitors ? can reduce a person's "viral burden" to very low levels and in many cases delay the progression of HIV disease for prolonged periods. However, antiretroviral regimens have yet to completely and permanently suppress the virus in HIV-infected people. Recent studies have shown that HIV persists in a replication-competent form in resting CD4+ T cells even in patients receiving aggressive antiretroviral therapy who have no easily detectable HIV in their blood. Investigators around the world are working to develop the next generation of anti-HIV drugs.

Although HIV-infected individuals often exhibit an extended period of clinical latency with little evidence of disease, the virus is never truly latent. NIAID researchers have shown that even early in disease, HIV actively replicates within the lymph nodes and related organs, where large amounts of virus become trapped in networks of specialized cells with long, tentacle-like extensions. These cells are called follicular dendritic cells (FDCs). 

FDCs are located in hot spots of immune activity called germinal centers. They act like flypaper, trapping invading pathogens (including HIV) and holding them until B cells come along to initiate an immune response.

Close on the heels of B cells are CD4+ T cells, which rush into the germinal centers to help B cells fight the invaders. CD4+ T cells, the primary targets of HIV, may become infected as they encounter HIV trapped on FDCs. Research suggests that HIV trapped on FDCs remains infectious, even when coated with antibodies. Thus, FDCs are an important reservoir of HIV, and the large quantity of infectious HIV trapped on FDCs may explain in part how the momentum of HIV infection is maintained

Once infected, CD4+ T cells may leave the germinal center and infect other CD4+ cells that congregate in the region of the lymph node surrounding the germinal center.

Over a period of years, even when little virus is readily detectable in the blood, significant amounts of virus accumulate in the germinal centers, both within infected cells and bound to FDCs. In and around the germinal centers, numerous CD4+ T cells are probably activated by the increased production of cytokines such as TNF-alpha and IL-6, possibly secreted by B cells. Activation allows uninfected cells to be more easily infected and increases replication of HIV in already infected cells. 

While greater quantities of certain cytokines such as TNF-alpha and IL-6 are secreted during HIV infection, others with key roles in the regulation of normal immune function may be secreted in decreased amounts. For example, CD4+ T cells may lose their capacity to produce interleukin 2 (IL-2), a cytokine that enhances the growth of other T cells and helps to stimulate other cells' response to invaders. Infected cells also have low levels of receptors for IL-2, which may reduce their ability to respond to signals from other cells. 

Breakdown of FDC networks. Ultimately, accumulated HIV overwhelms the FDC networks. As these networks break down, their trapping capacity is impaired, and large quantities of virus enter the bloodstream. 

Although it remains unclear why FDCs die and the FDC networks dissolve, some scientists think that this process may be as important in HIV pathogenesis as the loss of CD4+ T cells. The destruction of the lymph node structure seen late in HIV disease may preclude a successful immune response against not only HIV but other pathogens as well. This devastation heralds the onset of the opportunistic infections and cancers that characterize AIDS. 

CD8+ T cells are important in the immune response to HIV during the acute infection and the clinically latent stage of disease. These cells attack and kill infected cells that are producing virus. 

CD8+ T cells also appear to secrete soluble factors that suppress HIV replication. Several molecules, including RANTES, MIP-1alpha, MIP-1beta, and MDC appear to block HIV replication by occupying the co-receptors necessary for the entry of many strains of HIV into their target cells. There may be many other immune system molecules ? yet undiscovered ? that can suppress HIV replication to some degree.

HIV replicates rapidly; several billion new virus particles may be produced every day. In addition, the HIV reverse transcriptase enzyme makes many mistakes while making DNA copies from HIV RNA. As a consequence, many variants of HIV develop in an individual, some of which may escape destruction by antibodies or killer T cells. Additionally, HIV can recombine with itself to produce a wide range of variants or strains.

During the course of HIV disease, viral strains emerge in an infected individual that differ widely in their ability to infect and kill different cell types, as well as in their rate of replication. Scientists are investigating why strains of HIV from patients with advanced disease appear to be more virulent and infect more cell types than strains obtained earlier from the same individual. 

Researchers around the world are studying how HIV destroys or disables CD4+ T cells, and many think that a number of mechanisms may occur simultaneously in an HIV-infected individual. Recent data suggest that billions of CD4+ T cells may be destroyed every day, eventually overwhelming the immune system's regenerative capacity. 

Direct cell killing. Infected CD4+ T cells may be killed directly when large amounts of virus are produced and bud off from the cell surface, disrupting the cell membrane, or when viral proteins and nucleic acids collect inside the cell, interfering with cellular machinery.

Syncytia formation. Infected cells also may fuse with nearby uninfected cells, forming balloon-like giant cells called syncytia. In test-tube experiments at NIAID and elsewhere, these giant cells have been associated with the death of uninfected cells. The presence of so-called syncytia-inducing variants of HIV has been correlated with rapid disease progression in HIV-infected individuals. 

Apoptosis. Infected CD4+ T cells may be killed when cellular regulation is distorted by HIV proteins, probably leading to their suicide by a process known as programmed cell death or apoptosis. Recent reports indicate that apoptosis occurs to a greater extent in HIV-infected individuals, both in the bloodstream and lymph nodes.

Uninfected cells also may undergo apoptosis. Investigators have shown in cell cultures that the HIV envelope alone or bound to antibodies sends an inappropriate signal to CD4+ T cells causing them to undergo apoptosis even if not infected by HIV. 

Innocent bystanders. Uninfected cells may die in an innocent bystander scenario: HIV particles may bind to the cell surface, giving them the appearance of an infected cell and marking them for destruction by killer T cells.

Killer T cells also may mistakenly destroy uninfected cells that have consumed HIV particles and that display HIV fragments on their surfaces. Alternatively, because HIV envelope proteins bear some resemblance to certain molecules that may appear on CD4+ T cells, the body's immune responses may mistakenly damage such cells as well.

Anergy. Researchers have shown in cell cultures that CD4+ T cells can be turned off by a signal from HIV that leaves them unable to respond to further immune stimulation. This inactivated state is known as anergy.

Superantigens. Other investigators have proposed that a molecule known as a superantigen, either made by HIV or an unrelated agent, may stimulate massive quantities of CD4+ T cells at once, rendering them highly susceptible to HIV infection and subsequent cell death. 

Damage to Precursor Cells. Studies suggest that HIV also destroys precursor cells that mature to have special immune functions, as well as the parts of the bone marrow and the thymus needed for the development of such cells. These organs probably lose the ability to regenerate, further compounding the suppression of the immune system.

Although monocytes and macrophages can be infected by HIV, they appear to be relatively resistant to killing. However, these cells travel throughout the body and carry HIV to various organs, especially the lungs and brain. People infected with HIV often experience abnormalities in the central nervous system. Neurologic manifestations of HIV disease, seen in 40 to 50 percent of HIV-infected people, are the subject of many research projects. Investigators have hypothesized that an accumulation of HIV in brain and nerve cells, or the inappropriate release of cytokines or toxic byproducts by these cells, may be to blame.

During a normal immune response, many components of the immune system are mobilized to fight an invader. CD4+ T cells, for instance, may quickly proliferate and increase their cytokine secretion, thereby signalling other cells to perform their special functions. Scavenger cells called macrophages may double in size and develop numerous organelles, including lysosomes that contain digestive enzymes used to process ingested pathogens. Once the immune system clears the foreign antigen, it returns to a relative state of quiescence.

Paradoxically, although it ultimately causes immune deficiency, HIV disease for most of its course is characterized by immune system hyperactivation, which has negative consequences. As noted above, HIV replication and spread are much more efficient in activated CD4+ cells. Chronic immune system activation during HIV disease may also result in a massive stimulation of a person's B cells, impairing the ability of these cells to make antibodies against other pathogens.

Chronic immune activation also can result in apoptosis, and an increased production of cytokines that may not only increase HIV replication but also have other deleterious effects. Increased levels of TNF-alpha, for example, may be at least partly responsible for the severe weight loss or wasting syndrome seen in many HIV-infected individuals.

The persistence of HIV and HIV replication probably plays an important role in the chronic state of immune activation seen in HIV-infected people. In addition, researchers have shown that infections with other organisms activate immune system cells and increase production of the virus in HIV-infected people. Chronic immune activation due to persistent infections, or the cumulative effects of multiple episodes of immune activation and bursts of virus production, likely contribute to the progression of HIV disease.

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 fact sheets 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.

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. 

NIAID, a component of the National Institutes of Health, supports research on AIDS, tuberculosis and other infectious diseases as well as allergies and immunology.

Prepared by: 
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
February 1998