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Successful infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile, reverse transcripts. In the present study, we isolated highly purified quiescent T cells and utilized the CD3/CD28 activation pathways as well as cell cycle inhibitors to further define the role of costimulation and cell cycle progression in HIV-1 reverse transcription. Activation with αCD3 alone resulted in cell cycle progression into only G1 a and incomplete HIV-1 reverse transcription. Costimulation through the CD28 receptor and transition into G1 b was required to efficiently complete the reverse transcription process. These findings have relevance to immune activation in vivo, since lymphocytes rendered anergic by a single activation signal would be nonpermissive for productive infection with HIV-1. Importantly, these data also suggest that HIV vector-based genetic transduction strategies might be successful only in target cells that transition into the G1 b phase of the cell cycle.

journal of virology

Progression to the G<sub>1</sub>b Phase of the Cell Cycle Is Required for Completion of Human Immunodeficiency Virus Type 1 Reverse Transcription in T Cells

Progression to the G1b Phase of the Cell Cycle Is Required for Completion of Human Immunodeficiency Virus Type 1 Reverse Transcription in T Cells

Progression to the G₁b Phase of the Cell Cycle Is Required for Completion of Human Immunodeficiency Virus Type 1 Reverse Transcription in T Cells