HIV-1 replication is controlled at the level of T cell activation and proviral integration

M. Stevenson, T. L. Stanwick, M. P. Dempsey, C. A. Lamonica

Research output: Contribution to journalArticlepeer-review

620 Scopus citations

Abstract

During progression of the Acquired Immune Deficiency Syndrome (AIDS), the human immunodeficiency virus type 1 (HIV-1) is harbored in CD4+ T cells, which act as the primary reservoir for the virus. In vitro, HIV-1 requires activated T cells for a productive infection; however, in vivo, the number of circulating T cells in the activated state that are potential targets for HIV-1 infection is low. We have investigated the ability of HIV-1 to infect resting T cells, and the consequences of such an infection. T cell activation was not required for HIV-1 infection; however, viral DNA was unable to integrate in resting T cells and was maintained extrachromosomally. Subsequent T cell activation allowed integration of extrachromosomal forms and led to a productive viral life cycle. Extrachromosomal forms of viral DNA were found to persist for several weeks after infection of resting T cells and, following T cell activation, these forms maintained their ability to integrate and act as a template for infectious virus. Several lines of evidence, including temporal analysis of HIV-1 replication and analysis of an HIV-1 integrase deletion mutant, indicated that extra-chromosomal HIV-1 DNA genomes were transcriptionally active. These results are compatible with a model whereby HIV-1 can persist in a non-productive extra-chromosomal state in resting T cells until subsequent antigen-induced or mitogen-induced T cell activation, virus integration and release. Thus agents that induce T cell activation may control the rate of HIV-1 replication and spread during AIDS progression.

Original languageEnglish (US)
Pages (from-to)1551-1560
Number of pages10
JournalEMBO Journal
Volume9
Issue number5
DOIs
StatePublished - 1990
Externally publishedYes

Keywords

  • HIV-1 replication
  • Integration
  • Polymerase chain reaction
  • Resting CD4 lymphocytes
  • T cell activation

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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