HIV-1 Nef and Vpu interfere with L-selectin (CD62L) cell surface expression to inhibit adhesion and signaling in infected CD4+ T lymphocytes

Lia Vassena, Erica Giuliani, Herwig Koppensteiner, Sebastian Bolduan, Michael Schindler, Margherita Doria

Research output: Contribution to journalArticle

Abstract

Leukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+ T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+ T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+ T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses.

Original languageEnglish
Pages (from-to)5687-5700
Number of pages14
JournalJournal of Virology
Volume89
Issue number10
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'HIV-1 Nef and Vpu interfere with L-selectin (CD62L) cell surface expression to inhibit adhesion and signaling in infected CD4<sup>+</sup> T lymphocytes'. Together they form a unique fingerprint.

  • Cite this