Journal
VIROLOGY
Volume 372, Issue 2, Pages 300-312Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2007.11.007
Keywords
HIV-1; transcription; unintegrated HIV DNA; 1-LTR circle; 2-LTR circle; macrophage; nef; chemokine
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
- NIAID NIH HHS [R21 AI069981-01A2, AI069981, R21 AI069981] Funding Source: Medline
- NINDS NIH HHS [R21 NS051130-01A1, R21 NS051130-02, R21 NS051130, NS051130] Funding Source: Medline
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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. (c) 2007 Elsevier Inc. All rights reserved.
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