Defining the Key Targets of HIV Infection       

By Jeffrey Laurence, M.D.

Dr. Nicolas Chomont

March 2010—Although antiretroviral treatment can be extremely effective in lowering the level of HIV in the blood to a point where it cannot be detected by standard tests, the virus stubbornly persists in certain immune cells. In these infected T cells, it lies dormant, below the radar of the immune system or anti-HIV drugs.

amfAR fellow Dr. Nicolas Chomont is making important strides in precisely defining the nature of these cells, which are a key focus of efforts to develop a cure for HIV. Writing in the February issue of Journal of Immunology, Chomont and colleagues at the University of Montreal, McGill University, and Harvard build upon their prior work characterizing subsets of CD4+ T cells responsible for both HIV growth and dormancy. They had previously discovered that a long-lived “central memory” T cell is the major HIV reservoir in people who respond well to anti-HIV drugs and exhibit normal T-cell counts as a result of treatment. By contrast, those individuals in whom HAART blocks detectable virus growth but whose T-cell counts remain low have a different major viral reservoir in the “transitional memory” cell.

Why is this knowledge important? If researchers could pin a unique tag or address on those T-cell subsets responsible for establishing different types of reservoirs, they might be able to develop a way to target them selectively and destroy them. They might also be able to design a means of blocking the “homing instinct” of infected cells, which are drawn to key anatomic sites of the body, such as the brain and intestines.

Chomont and associates now report that only two types of CD4+ T cells are highly susceptible to HIV infection and active growth. They have labeled these T cells either CCR4+CCR6+ or CXCR3+CCR6+, based upon the type of homing or chemokine receptor they bear—CCR4 or CXCR3. Both types of cells express CCR6, the receptor for two soluble proteins underlying our natural defenses against infection: CCL20 and the beta-defensins. The scientists also discovered that these cells have the potential to infiltrate and recruit additional CCR6-bearing T cells into lymph nodes, vaginal tissues, the intestines, and the brain.

Chomont and associates have exposed CCR6 as a novel target for future study and possibly for treatment. They concluded that “It is necessary that new therapeutic strategies against HIV interfere with viral replication/persistence in discrete CCR6+ T cell subsets.”

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