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

Erica Giuliani, Lia Vassena, Silvia Galardi, Alessandro Michienzi, Maria Giovanna Desimio, Margherita Doria

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalVirology
Volume523
DOIs
Publication statusPublished - Oct 2018

Keywords

  • Ataxia Telangiectasia Mutated Proteins/genetics
  • CD4-Positive T-Lymphocytes/metabolism
  • G2 Phase Cell Cycle Checkpoints/genetics
  • Gene Expression Regulation
  • HIV-1/genetics
  • Histones/genetics
  • Host-Pathogen Interactions
  • Human Immunodeficiency Virus Proteins/genetics
  • Humans
  • Jurkat Cells
  • L-Selectin/genetics
  • Primary Cell Culture
  • RNA, Messenger/genetics
  • Signal Transduction
  • Viral Regulatory and Accessory Proteins/genetics
  • nef Gene Products, Human Immunodeficiency Virus/genetics
  • vif Gene Products, Human Immunodeficiency Virus/genetics
  • vpr Gene Products, Human Immunodeficiency Virus/genetics

Fingerprint Dive into the research topics of 'Dual regulation of L-selectin (CD62L) by HIV-1: Enhanced expression by Vpr in contrast with cell-surface down-modulation by Nef and Vpu'. Together they form a unique fingerprint.

  • Cite this