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J. Virol. doi:10.1128/JVI.02569-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

IMMEDIATE ACTIVATION FAILS TO RESCUE EFFICIENT HIV REPLICATION IN QUIESCENT CD4⁺ T CELLS

Department of Medicine, Division of Hematology&Oncology, Department of Molecular and Medical Pharmacology, Department of Microbiology, Immunology and Molecular Genetics, and UCLA AIDS Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA

^* To whom correspondence should be addressed. Email: jzack{at}ucla.edu.

	Abstract

Unlike activated T cells, quiescent CD4⁺ T cells have shown resistance to human immunodeficiency virus (HIV) infection due to a block in the early events of the viral life cycle. To further investigate the nature of this block, we infected quiescent CD4⁺ T cells with HIV-1_NL4-3 and immediately stimulated them. Compared to activated (pre-stimulated) cells, these post-stimulated cells showed slightly decreased viral entry and delays in the completion of reverse transcription. However, relative efficiency of integration was similar to that of pre-stimulated cells. Together this resulted in decreased expression of tat/rev mRNA and synthesis of viral protein. Furthermore, based on cell cycle staining and BrdU incorporation, post-stimulated cells expressing viral protein failed to initiate a second round of their cell cycle, independent of Vpr mediated arrest. Together, these data demonstrate that the early stages of the HIV life cycle are inefficient in these post-stimulated cells, and that efficient replication cannot be induced by subsequent activation.

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