Ailments and Situations - Acquired Immune Deficiency Syndrome or AIDS - HIV and CD4

Note: This section explains the physiological aspects of HIV & CD4 interaction and is quite technical. You may skip this section and continue with Symptoms and Signs, which follows.

HIV infects cells that have the CD4 receptor on their cell membrane. These receptors are found in high numbers on T helper cells/lymphocytes, i.e., CD4+ T cells/lymphocytes, which are the primary target of HIV.

CD4+ T cells comprise 60 to 70 percent of all circulating T cells. T cells collectively confir what is called cell-mediated immunity. CD4+ T cells respond to foreign particles (antigens) that have bound to the surface of macrophages and B cells. The CD4 receptors on the T cells bind to other specific molecules that are normally found on the surface of other immune system cells. This starts a cascade of reactions to fight the parasite that has infected the body. CD4+ T cells also produce growth factors to stimulate the proliferation and differentiation of B cells, stimulate antibody production, and release interlukin-2 (IL-2), which increases the activity of other types of T cells. Given their critical role in antigen defence, a reduction in the number of CD4+ T cells can have a profound effect on several components of the immune system and thus the integrity of the immune system as a whole.

HIV has molecules on its viral coat that are similar to the molecules on the cells that bind to CD4 receptors. These HIV molecules are called gp120. Once the viral gp120 molecule has bound with the CD4 receptor on the surface of a host cell, another protein on the viral coat, gp41initiates fusion of the two surfaces. At this point, HIV RNA and reverse transcriptase are released into the host cell. This process can occur between HIV and any cell that carries the CD4 receptor on its surface.

As mentioned above, CD4+ T cells carry this receptor and are the primary target for HIV. Other cells carry this receptor as well, including monocytes, macrophages, some B cells, and even some brain and intestinal cells. Brain and intestinal cells, however, express very few CD4 molecules on their cell surface. Monocytes and macrophages are not killed by HIV and are thought to act as reservoirs for the virus. It is also believed that monocyte infection plays an integral role in the entry of HIV into the brain, causing neurological symptoms. The infection of CD4+ T cells ultimately causes the destruction of the immune system and resulting impaired defences against viruses, fungi, parasites and certain bacteria. This situation leaves AIDS patients in a life-threatening situation.

It is not known what causes latent state HIV to become active. Exactly how HIV reduces CD4+ T cell numbers is also unknown, but some theories exist. One theory proposes that infected cells begin to process HIV genetic information and start to express the gp120 protein on the cell surface. The gp120 protein on the surface of these T cells then attach to CD4 molecules on the surface of uninfected T cells. The membranes fuse and another T cell is infected. Eventually, many cells fuse to produce multinucleated giant cells called syncitia. One HIV-infected T cell may eventually bind and fuse with up to 50 uninfected T cells. After giant cell formation occurs, the cells lose immune function and die.

A second theory focuses on the destruction of the thymus gland by HIV. The thymus gland is typically not a major source of T cells in adults, but it is theorized that when T cell numbers are very low, the thymus becomes important in replacing them. If the thymus is destroyed, T cells cannot be replenished when numbers drop.

A third theory proposes that HIV kills the CD4+ T cell directly or makes them a target for other immune cells to destroy. This most likely occurs in lymphoid tissue. In addition, the virus can shed free gp120 proteins into circulation which can bind to CD4+ T cells. They then become activated, express the viral protein on their cell surface, and are targeted and destroyed by other cells of the immune system.

It seems most likely that an overall process combining all three theories causes the CD4+ T cell decline, leading to the ultimate destruction of the immune system. Thus, HIV causes a persistent infection with a low level of activity throughout most of its course, during which you are almost asymptomatic.