Journal
VIROLOGY
Volume 355, Issue 2, Pages 127-137Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2006.07.020
Keywords
CD4+T-lymphocytes; feeder cells; long-term survival; quiescent cells; latent HIV infection
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Funding
- NIAID NIH HHS [R21 AI066999] Funding Source: Medline
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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 (similar to 1-10 cells per 10(6) CD4+ T-cells). To circuinvent 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 similar to 5 x 10(4) latently infected cells per 10(6) cells in culture, which is similar to 10(3)- to 10(4)-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. (c) 2006 Elsevier Inc. All rights reserved.
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