Productive infection of double-negative T cells with HIV in vivo. Academic Article uri icon

Overview

abstract

  • HIV induces CD4 down-regulation from the surface of infected cells by several independent mechanisms, suggesting an important biological role for this phenomenon. In vitro CD4 down-regulation generates T cells with a double-negative (DN) CD4(-)CD8(-) T cell receptor-alphabeta(+) phenotype. However, evidence that this down-regulation occurs in vivo in HIV-infected subjects is lacking, and viral load or viral production assays invariably focus on CD4(+) T cells. We show here that HIV infection can often be detected in sorted DN cells from peripheral blood and lymph nodes, even when plasma viral load is undetectable. DN T cells infected with HIV represented up to 20% of the cellular viral load in T cells, as determined by DNA PCR. In patients on successful highly active antiretroviral therapy, the viral load decreased in the plasma in CD4(+) and in DN T cells, suggesting that infected DN cells, like CD4(+) cells, contribute to viral production and are sensitive to highly active antiretroviral therapy. Indeed, HIV unspliced and multispliced RNAs were often detectable in DN T cells in spite of the small size of this subset. Infectious virus from DN T cells was transmitted efficiently in coculture experiments with uninfected T cell lymphoblasts, even when viral DNA in the DN cells was barely detectable. We conclude that a discrete population of infected DN T cells exists in HIV-positive subjects, even when the plasma viral load is undetectable. These cells may represent an important source of infectious virus.

publication date

  • October 12, 1999

Research

keywords

  • DNA, Viral
  • HIV
  • HIV Infections
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC18394

Scopus Document Identifier

  • 0032716110

Digital Object Identifier (DOI)

  • 10.1073/pnas.96.21.11958

PubMed ID

  • 10518558

Additional Document Info

volume

  • 96

issue

  • 21