November 6, 2002
"The immune system needs to evolve along with the virus, and this evolution becomes difficult because it is in a milieu of immune deficiency," researcher Premlata Shankar told UPI. While the immune system's memory-based component might continue to resist the strain of HIV it first encountered -- or strains used in laboratory tests -- subsequent viral mutations weaken its ability to mount an effective defense.
The researchers reported their findings in the article "The Functional CD8 T Cell Response to HIV Becomes Type-Specific in Progressive Disease" in the November issue of the Journal of Clinical Investigation (2002;110:1339-1347).
HIV's ability to mutate is well-documented, but the effects of those mutations on an infected individual have not been thoroughly studied. In examining the immune system's killer cell responses to mutated forms of HIV taken from people at different stages of HIV infection, the researchers found that killer cells from patients with more advanced infections could not destroy the mutated virus, even though they could still neutralize common laboratory strains. But killer cells from people with less-advanced HIV could destroy both the lab strains and their own mutated forms.
According to immunologist Beth Jamieson of the University of California-Los Angeles' David Geffen School of Medicine, "The side-by-side comparison of cellular responses to laboratory strains and autologous [mutated after infection] strains at different stages is new. This shows that the response to virus is lost later in infection. Now we need to know why."
When a person is first infected with HIV, the immune system produces CD8-T killer and CD4-T helper cells. The system remembers the type of molecules on the surface of the attacking virus, so the next time the system encounters the virus, it produces, from memory, many cells to attack it again. But when the virus mutates, the immune system is no longer able to identify and kill the mutations. The researchers also found that much of the deficiency occurs because HIV destroys the helper cells, stopping the efficient production of new killer cells and helping weaken those that are produced. Because of this finding, Jamieson recommended further research "looking at the epitopes [surface proteins] on the virus over time in individuals."
"While there are no direct implications for diagnosis or treatment, an important motivation for this sort of study is the development of knowledge that could lead to successful HIV vaccines, both to prevent and to treat HIV infection," infectious disease specialist Stuart Ray, of the Johns Hopkins University School of Medicine in Baltimore, told UPI.