HIV's Alternative Modus Operandi?

PARK CITY, UTAH--Since the early 1980s researchers have known that the AIDS virus wreaks havoc on the body's defenses by destroying immune system cells called CD4 T lymphocytes--so-called because of the CD4 protein that studs their surface. HIV docks to CD4 before slipping inside a cell. But work presented here yesterday at the HIV Pathogenesis and Treatment meeting--and results reported in tomorrow's Proceedings of the National Academy of Sciences (PNAS)--suggest that a second key immune cell could also be an important target for HIV.

A team led by Carl June at the Naval Medical Research Institute in Bethesda, Maryland, and Guy Delespesse of the University of Montreal reported that HIV can also infect T cells bearing a protein called CD8. These cells are thought to help suppress HIV infection in early stages of infection, but eventually the CD8 cells lose this ability and the patient progresses to full-blown AIDS. The team isolated CD8 cells from umbilical cord blood of newborns and "activated" them with compounds that artificially stimulate an immune response--a prerequisite to infection by HIV, which attacks only activated immune cells. The cells began to express CD4 on their surfaces as well as CD8, making them vulnerable to HIV. The findings are in press at the Journal of Experimental Medicine. A second team, led by Jerome Zack of the UCLA School of Medicine, reported similar results at the meeting, and a group led by Robert Gallo of the Institute of Human Virology in Baltimore report in PNAS that they have seen the same phenomenon in adult CD8 cells.

The researchers argue that if badly needed CD8 cells succumb to HIV infection, that may explain in part why patients eventually fail to control their infection. Moreover, June says, his team's work could shed light on why children progress to full-blown AIDS more quickly than adults: They have a larger proportion of "naive" CD8 cells that have not yet encountered foreign invaders; these unchallenged cells were found to be more likely to express CD4 than were so-called "memory cells" that have been exposed to foreign antigens.

"This is an important in vitro finding and might represent an important mechanism for viral persistence in this cell population," says immunologist Luis Montaner of the Wistar Institute in Philadelphia. But Montaner and other researchers who spoke to ScienceNOW warned against extrapolating these results to infected people. One concern is that cells "taken out of their normal context" might fail to produce biochemical "silencers" that are known to suppress CD4 expression in CD8 cells, says immunologist Daniel Littman of New York University. But if the findings hold up after further study, says Littman, this vulnerability of CD8 cells "would probably have a negative impact on the immune response against the virus."

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