Expression pattern of HIV-1 coreceptors on T cells: Implications for viral transmission and lymphocyte homing

The potential for understanding the mechanism of immune system damage by HIV-1 received an enormous boost last year, when it was discovered that several specific chemokine receptors are used by HIV-1 as coreceptors for entry into target cells (1–5). It had been known for close to a decade that the expression of human CD4, the high-affinity receptor for HIV-1, was necessary but not sufficient for viral entry and that a species-specific cofactor might also be required (6–8). The long-awaited identification of the cofactors fused the seemingly disparate areas of chemokine and HIV research and has fueled extraordinary progress in a short period of time. The recent discoveries not only provide insight into the mechanism of viral entry, but also hold the promise to explain the mechanism by which early viremia progresses to immunodeficiency. At the heart of this problem lies the paradox of why strains of virus involved in transmission of infection differ in their specificity for chemokine receptors from strains found late in disease progression. In this issue of the Proceedings, Bleul et al. (9) report on the expression patterns of the two principal HIV-1 coreceptors on T cell subsets and thus provide a potential clue toward resolving the mystery of the evolving cellular tropism of HIV-1 at different stages of infection.

The recent work follows up on studies performed during the last 6 years that had demonstrated the existence of distinct cellular tropisms of different strains of HIV-1. Most primary isolates of HIV-1, present throughout the course of infection, are able to infect macrophages and primary T cells, but not transformed T cell lines (designated as M-tropic strains). In contrast, strains of HIV-1 that have been adapted to grow in transformed T cell lines show a similar tropism to those that emerge in …