A novel in vitro system to generate and study latently HIV-infected long-lived normal CD4+ T-lymphocytes

Gautam K. Sahu, Kyeongeun Lee, Jiaxiang Ji, Vivian Braciale, Samuel Baron, Miles W. Cloyd

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Studies of mechanisms of HIV-latency and its reactivation in long-lived resting CD4+ T-lymphocytes in patients have been limited due to the very low frequency of these cells (∼ 1-10 cells per 106 CD4+ T-cells). To circumvent this obstacle, an in vitro culture system for post-activation long-term survival of normal CD4+ T-cells in a quiescent (non-cycling) state was developed and used to generate latently infected, long-lived quiescent CD4+ T-cells from HIV-infected, activated normal CD4+ T-lymphocytes. This yielded a frequency of ∼ 5 × 104 latently infected cells per 106 cells in culture, which is ∼ 103- to 104-fold higher than that available from patients. Moreover, 5-10% of long-term surviving non-cycling T-cells were found to make infectious HIV continuously at low levels, showing that HIV production from infected T-cells does not require full cellular activation. This model system should facilitate studies of long-lived, latently infected and persistently HIV-producing quiescent normal CD4+ T-lymphocytes.

Original languageEnglish (US)
Pages (from-to)127-137
Number of pages11
JournalVirology
Volume355
Issue number2
DOIs
StatePublished - Nov 25 2006

Keywords

  • CD4+ T-lymphocytes
  • Feeder cells
  • Latent HIV infection
  • Long-term survival
  • Quiescent cells

ASJC Scopus subject areas

  • Virology

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