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Journal of Virology, November 2005, p. 14179-14188, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14179-14188.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Can Establish Latent Infection in Resting CD4⁺ T Cells in the Absence of Activating Stimuli

Departments of Medicine,¹ Pathology and Laboratory Medicine, Division of Transfusion Medicine, University of Pennsylvania,² Department of Decision Sciences, Drexel University, Philadelphia, Pennsylvania³

Received 31 May 2005/ Accepted 9 August 2005

Resting CD4⁺ T cells are the best-defined reservoir of latent human immunodeficiency virus type 1 (HIV-1) infection, but how the reservoir is formed is unclear. Understanding how the reservoir of latently infected cells forms is critical because it is a major barrier to curing HIV infection. The system described here may provide an in vitro model of latent HIV-1 infection in resting CD4⁺ T cells. We demonstrated that HIV-1 integrates into the genomes of in vitro-inoculated resting CD4⁺ T cells that have not received activating stimuli and have not entered cell cycle stage G_1b. A percentage of the resting CD4⁺ T cells that contain integrated DNA produce virus upon stimulation, i.e., are latently infected. Our results show that latent HIV-1 infection occurs in unstimulated resting CD4⁺ T cells and suggest a new route for HIV-1 reservoir formation.

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