Researchers have learned important details of how the immune system first controls HIV, and how the virus evades it, through a study in monkeys published this week in Nature.(1, 2)
For some time it has been widely believed that a kind of T cell called cytotoxic T lymphocyte (CTL) is particularly important in controlling HIV. The new study investigated how this works by infecting monkeys with a precisely known strain of SIV, a virus which causes an infection in monkeys comparable in many ways to AIDS in humans. Because the infecting virus was well known, changes in the virus during infection could be observed.
The researchers found that most of the SIV-specific CTLs, which the monkeys produced in response to the infection, recognized peptides (short sequences of amino acids) from either the Tat or Gag "regulatory" proteins of the virus. And after 8 weeks, all of the original virus was gone -- showing the effect of the immune response. But the original virus had been replaced by SIV with small changes, usually in Tat. So apparently the body is able to control the virus through Tat-specific CTLs -- but the virus can mutate and change its Tat, getting around this immune control.
There are several biological reasons for believing that an immune response directed against Tat (or possibly Gag) may be particularly effective in controlling HIV. First, these proteins are less able to change than other parts of HIV; some parts of tat might not be able to change without making a virus which could not sustain an infection, and if so, a preventive or treatment vaccine could be directed against them. Also, Tat is produced early in the life cycle of HIV -- before the virus has had time to suppress immune responses through other mechanisms. And the immune escape found in this study may be less of an issue with a preventive vaccine, since there is much less viral variation and less chance to produce new mutations. And in any case, the new vaccine ideas suggested by this study are readily testable.
Other research groups have already been working on a Tat-based vaccine.
Anthony Fauci, M.D., director of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), which funded the research, said, "These animal studies open the window on immune events in early HIV infection and provide a rationale for exploring a new approach to designing HIV vaccines. The results suggest that using vaccines that stimulate immune responses against virus proteins produced within a few hours after infection, such as Tat, may help to control HIV."
A separate in-depth explanation of the results and their significance was published in the same issue of the journal.(2)
Allen TM, O'Connor DH, Jing P and others. Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia. Nature. September 21, 2000; volume 407, pages 386-390.
Walker BD and Goulder PJR. Escape from the immune system. Nature. September 21, 2000; volume 407, pages 313- 314.
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Copyright 2000 by John S. James. Permission granted for noncommercial reproduction, provided that our address and phone number are included if more than short quotations are used.
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