possible that Tat secretion initiates a spate of viral reproduction in previously latently infected cells. In addition, there are some indications that Tat may directly kill uninfected cells. Alternatively, Tat may also alter the chemical signals that are sent out from a helper T-cell. According to this theory, the altered signals result in an immune response that is ineffective or inappropriate. For example, there may be too many signals stimulating antibody production and not enough stimulating killer T-cell activity, so that while there is an immune response it is ineffectual and does not eliminate the virus.

New evidence has come to light to suggest that the Net protein may also be secreted. Some scientists think that Nef may act as a so-called superantigen. Superantigens are thought not to depress immune activity but to overstimulate it. As a consequence, the immune system starts to look like a ''Keystone Cops" episode where the perpetrator slips past a frenzied and disorganized immune system.

It is important to note that many of these phenomena are studied in the laboratory using viruses and immune cells that have been cultured outside the human hosts from which they were taken. The artificial circumstances of culture conditions may well alter some of the biochemistry of these entities, and scientists caution that the behavior of cells and viruses may be different in intact living systems.

So the question of whether the laboratory situation realistically reproduces real life must be addressed by scientists hoping to understand the relationship between HIV and AIDS. But even if all of these phenomena occur in a person with AIDS, scientists must also assess which mechanisms are of primary importance in helper T-cell death and which are fairly minor contributors. New evidence comes to light almost daily that makes the research community evaluate these questions in a new way. Some scientists believe that as the virus replicates within a host new strains emerge that are more efficient killers, more aggressive at reproducing, and more effective at infecting cells than its progenitors. Those who believe this suggest that the emergence of these potent new strains accounts for the sudden and rapid decline of the immune system after 10 or more years of calm.

As research techniques improve, scientists discover aspects of the interaction they could not previously discern. For example, using higher-resolution techniques, some research groups are finding that many more than 1 percent of helper T-cells are actually infected with HIV. New estimates suggest that 20 to 30 percent may be infected at any one time. Some researchers think these numbers are adequate to explain the observed loss of helper cells. In that case the indirect mechanisms of

The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement