Human macrophages support persistent transcription from unintegrated HIV-1 DNA

Journal Article · Sat Mar 15 04:00:00 EDT 2008 · Virology

DOI:https://doi.org/10.1016/j.virol.2007.11.007· OSTI ID:21078030

Kelly, Jeremy ^[1]; Beddall, Margaret H ^[2]; Dongyang, Yu; Iyer, Subashini R ^[1]; Marsh, Jon W ^[2]; Yuntao, Wu ^[1]

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1. Department of Molecular and Microbiology, George Mason University, Manassas, Virginia 20110 (United States)
2. Section on Molecular Virology, Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, Maryland 20892 (United States)

Retroviruses require integration of their RNA genomes for both stability and productive viral replication. In HIV infection of non-dividing, resting CD4 T cells, where integration is greatly impeded, the reverse transcribed HIV DNA has limited biological activity and a short half-life. In metabolically active and proliferating T cells, unintegrated DNA rapidly diminishes with cell division. HIV also infects the non-dividing but metabolically active macrophage population. In an in vitro examination of HIV infection of macrophages, we find that unintegrated viral DNA not only has an unusual stability, but also maintains biological activity. The unintegrated linear DNA, 1-LTR, and 2-LTR circles are stable for at least 30 days. Additionally, there is persistent viral gene transcription, which is selective and skewed towards viral early genes such as nef and tat with highly diminished rev and vif. One viral early gene product Nef was measurably synthesized. We also find that independent of integration, the HIV infection process in macrophages leads to generation of numerous chemokines.

• OSTI ID: 21078030
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 372; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

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IN VITRO
MACROPHAGES
RNA
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