Dual regulation of L-selectin (CD62L) by HIV-1: Enhanced expression by Vpr in contrast with cell-surface down-modulation by Nef and Vpu

Abstract

The HIV-1 accessory protein Vpr displays various activities that can favor viral replication such as G₂ cell cycle arrest. Vpr also modulates host gene expression, although this property is poorly characterized. Here, we investigated the effect of Vpr on L-selectin (CD62L), which crucially controls leukocytes circulation and generation of immune responses against pathogens. We report that Vpr up-regulates CD62L mRNA level when individually expressed in Jurkat T cells as well as during HIV-1 infection of primary CD4⁺ T cells. Vpr mutant analysis and use of inhibitors suggest that the effect of Vpr on CD62L occurs independently of G₂ arrest but requires activation of the ATR kinase. Yet, induction of CD62L expression by Vpr is contrasted by down-regulation of CD62L protein by Nef that, together with Vpu, induces a net reduction of cell-surface CD62L on HIV-1-infected cells, which may impact viral spread and evasion of immune responses.

Keywords: ATR; CD62L; DDR; HIV-1; Nef; Vpr.