A Dual-Tropic Primary HIV-1 Isolate That Uses Fusin and the β-Chemokine Receptors CKR-5, CKR-3, and CKR-2b as Fusion Cofactors

TLDR

We demonstrate that the β‑chemokine receptor CKR‑5 acts as a cofactor for M‑tropic HIV viruses. CKR‑5 with CD4 enables syncytia formation and entry of M‑tropic but not T‑tropic viruses, and the dual‑tropic isolate 89.6 uses both Fusin and CKR‑5 as entry cofactors, while CKR‑3 and CKR‑2b support 89.6‑mediated syncytia but not other strains, implying T‑tropic viruses may evolve from M‑tropic strains by gaining multi‑cofactor usage.

Abstract

Here, we show that the β-chemokine receptor CKR-5 serves as a cofactor for M-tropic HIV viruses. Expression of CKR-5 with CD4 enables nonpermissive cells to form syncytia with cells expressing M-tropic, but not T-tropic, HIV-1 env proteins. Expression of CKR-5 and CD4 enables entry of a M-tropic, but not a T-tropic, virus strain. A dual-tropic primary HIV-1 isolate (89.6) utilizes both Fusin and CKR-5 as entry cofactors. Cells expressing the 89.6 env protein form syncytia with QT6 cells expressing CD4 and either Fusin or CKR-5. The β-chemokine receptors CKR-3 and CKR-2b support HIV-1 89.6 env-mediated syncytia formation but do not support fusion by any of the T-tropic or M-tropic strains tested. Our results suggest that the T-tropic viruses characteristic of disease progression may evolve from purely M-tropic viruses prevalent early in virus infection through changes in the env protein that enable the virus to use multiple entry cofactors.