HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8-like chemokine activity on monocytes through Rho/ROCK activation.

Exogenous HIV-1 matrix protein p17 was found to deregulate biological activities of many different immune cells that are directly or indirectly involved in AIDS pathogenesis after binding to unknown cellular receptor(s). In particular, it was found to induce a functional program in monocytes related to activation and inflammation. Here we demonstrate that CXCR1 is the receptor molecule responsible for p17 chemokine-like activity on monocytes. Following CXCR1 binding, p17 was capable of triggering rapid adhesion and chemotaxis of monocytes through a pathway which involved Rho/ROCK. Moreover, CXCR1 silenced primary monocytes lost, whereas CXCR1 transfected Jurkat acquired, responsiveness to p17 chemoattraction. Studies performed by Surface Plasmon Resonance confirmed the capacity of p17 to bind CXCR1 and showed that the p17/CXCR1 interaction occurred with a low affinity when compared to that measured for IL-8, the physiological CXCR1 ligand. In all its activities, p17 mimicked IL-8, the natural high affinity ligand of CXCR1. Recent reports have highlighted the role of IL-8 and CXCR1 in HIV-1 replication and AIDS pathogenesis. Our finding calls for an exploration of the therapeutic potential of blocking the p17/IL-8/CXCR1 axis in HIV-1 infection.