Occludin, caveolin-1, and Alix form a multi-protein complex and regulate HIV-1 infection of brain pericytes

Abstract

HIV-1 enters the brain by altering properties of the blood-brain barrier (BBB). Recent evidence indicates that among cells of the BBB, pericytes are prone to HIV-1 infection. Occludin (ocln) and caveolin-1 (cav-1) are critical determinants of BBB integrity that can regulate barrier properties of the BBB in response to HIV-1 infection. Additionally, Alix is an early acting endosomal factor involved in HIV-1 budding from the cells. The aim of the present study was to evaluate the role of cav-1, ocln, and Alix in HIV-1 infection of brain pericytes. Our results indicated that cav-1, ocln, and Alix form a multi-protein complex in which they cross-regulate each other's expression. Importantly, the stability of this complex was affected by HIV-1 infection. Modifications of the complex resulted in diminished HIV-1 infection and alterations of the cytokine profile produced by brain pericytes. These results identify a novel mechanism involved in HIV-1 infection contributing to a better understanding of the HIV-1 pathology and the associated neuroinflammatory responses.

Keywords: Alix; HIV-1; blood-brain barrier; caveolin-1; pericytes.