Tumor suppressor p21 found in abundance in people impervious to developing AIDS
VANCOUVER — A protein best known as a cancer suppressor may enable some people infected with HIV to fend off the virus indefinitely, a new study shows. Copious production of this protein, called p21, shows up in a select group of HIV-positive people who rarely develop AIDS, scientists reported October 21 at a meeting of the Infectious Diseases Society of America.
Some HIV patients, dubbed long-term nonprogressors, get infected with HIV yet seem impervious to its effects. While research has suggested factors that could separate these lucky few from most HIV patients, the specifics underlying their resistance are still an area of keen interest. “This is a specific group of patients who are spontaneously able to control HIV and don’t get sick from it,” says infectious disease physician Mathias Lichterfeld of Harvard Medical School and Massachusetts General Hospital in Boston, who presented the new data.
In the new study, researchers compared four groups of people — 14 who were HIV negative, 16 with HIV that had progressed, 10 with HIV who were undergoing treatment and 15 whose HIV infection had totally stalled. This last group included nonprogressors so adept at halting an HIV infection that they didn’t even have any virus detectable by routine tests. (Researchers ascertained infection by testing for antibodies to HIV.) Scientists call this subset of patients elite controllers. “They comprise 1 percent or fewer of HIV-infected people,” Lichterfeld says.
The researchers obtained immune cells called CD4 T cells — the prime targets of HIV — from all the volunteers and subjected these cells to lab tests. The tests showed that elite controllers had CD4 T cells that made 10 to 100 times more p21 than did people in the other three groups. “It’s not a subtle difference. It’s quite striking,” Lichterfeld says.
When the researchers put these cells in lab dishes and subjected them to an HIV assault, the cells loaded with p21 held off the virus.
"These data suggest that this protein can inhibit HIV,” Lichterfeld says. But he notes that the mechanism by which p21 does this and even how these cells make extra amounts of the protein are not yet fully understood. There may be genetic variations involved, he says.
“It might offer an alternative way to control HIV if we can find a way to manipulate this p21 protein in patients,” he says. But using p21 as a tool probably won’t be as simple as giving the protein to people.
“The fact that it occurs in nature is encouraging — that you have a natural model,” says Joel Gallant, an infectious disease physician who specializes in HIV at Johns Hopkins University in Baltimore. Although many questions need to be answered before finding a way to use p21 clinically, he says, “this could be critical someday in getting better control of HIV.”
M. Lichterfeld. CD4 T cells from HIV-1 elite controllers resist HIV-1 infections via p21. , Infectious Diseases Society of America 48th Annual Meeting, Vancouver, October 21, 2010. Abstract available: [Go to]
I. H. Chowdhury et al. HIV-1 Vpr Activates Cell Cycle Inhibitor p21/Waf1/Cip1: A Potential Mechanism of G2/M Cell Cycle Arrest. Virology, Vol. 305, January 20, 2010, p. 371. doi: 10.1006/viro.2002.1777
E. Grundner-Culemann et al. Is the 21 KD protein (p21) a prognostic marker in HIV-1-infection? International Conference on AIDS, Vol. 8, Jul 19-24, 1992 (abstract no. PoB 3475).