The V3 domain of the HIV–1 gp120 envelope glycoprotein is critical for chemokine–mediated blockade of infection
- 1 November 1996
- journal article
- research article
- Published by Springer Nature in Nature Medicine
- Vol. 2 (11), 1244-1247
- https://doi.org/10.1038/nm1196-1244
Abstract
The ability of CD8+ T cells derived from human immunodeficiency virus (HIV)–infected patients to produce soluble HIV–suppressive factor(s) (HIV–SF)1–3 has been suggested as an important mechanism of control of HIV infection in vivo4,5. The C–C chemokines RANTES, MlP–lα and MIP–lβ were recently identified as the major components of the HIV–SF produced by both immortalized and primary patient CD8+ T cells. Whereas they potently inhibit infection by primary and macrophage–tropic HIV–1 isolates, T–cell line–adapted viral strains tend to be insensitive to their suppressive effects6. Consistent with this discrepancy, two distinct chemokine receptors, namely, CXCR4 (ref. 7) and CCR5 (ref. 8), were recently identified as potential co–receptors for T–cell line–adapted and macrophage–tropic HIV–1 isolates, respectively9–12. Here, we demonstrate that the third hypervariable domain of the gp120 envelope glycoprotein is a critical determinant of the susceptibility of HIV–1 to chemokines. Moreover, we show that RANTES, MIP–1α and MIP–1β block the entry of HIV–1 into cells and that their antiviral activity is independent of pertussis toxin–sensitive signal transduction pathways mediated by chemokine receptors. The ability of the chemokines to block the early steps of HIV infection could be exploited to develop novel therapeutic approaches for AIDS.Keywords
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