CD8+ T cells promote HIV latency by remodeling CD4+ T cell metabolism to enhance their survival, quiescence, and stemness. Academic Article uri icon

Overview

abstract

  • HIV infection persists during antiretroviral therapy (ART) due to a reservoir of latently infected cells that harbor replication-competent virus and evade immunity. Previous ex vivo studies suggested that CD8+ T cells from people with HIV may suppress HIV expression via non-cytolytic mechanisms, but the mechanisms responsible for this effect remain unclear. Here, we used a primary cell-based in vitro latency model and demonstrated that co-culture of autologous activated CD8+ T cells with HIV-infected memory CD4+ T cells promoted specific changes in metabolic and/or signaling pathways resulting in increased CD4+ T cell survival, quiescence, and stemness. Collectively, these pathways negatively regulated HIV expression and ultimately promoted the establishment of latency. As shown previously, we observed that macrophages, but not B cells, promoted latency in CD4+ T cells. The identification of CD8-specific mechanisms of pro-latency activity may favor the development of approaches to eliminate the viral reservoir in people with HIV.

authors

  • Mutascio, Simona
  • Mota, Talia
  • Franchitti, Lavinia
  • Sharma, Ashish A
  • Willemse, Abigail
  • Bergstresser, Sydney N
  • Wang, Hong
  • Statzu, Maura
  • Tharp, Gregory K
  • Weiler, Jared
  • Sékaly, Rafick-Pierre
  • Bosinger, Steven E
  • Paiardini, Mirko
  • Silvestri, Guido
  • Jones, Brad
  • Kulpa, Deanna A

publication date

  • April 7, 2023

Research

keywords

  • HIV Infections

Identity

Scopus Document Identifier

  • 85153328247

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2023.03.010

PubMed ID

  • 37030290

Additional Document Info

volume

  • 56

issue

  • 5