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The Journal of Immunology, 2008, 181, 7713 -7720
Copyright © 2008 by The American Association of Immunologists, Inc.

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An In Vitro System to Model the Establishment and Reactivation of HIV-1 Latency

Alessandra Marini, Jill M. Harper and Fabio Romerio1

Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201

HIV-1 establishes latency primarily by infecting activated CD4+ T cells that later return to quiescence as memory cells. Latency allows HIV-1 to evade immune responses and to persist during antiretroviral therapy, which represents an important problem in clinical practice. The lack of a valid cellular model to study HIV-1 latency has hindered advances in the understanding of its biology. In this study, we attempted to model HIV-1 latency using human primary CD4+ T cells infected in vitro with HIV-1 after activation with Ag-loaded dendritic cells and then brought back to quiescence through a resting phase in the presence of IL-7. During the resting phase, expression of cellular activation markers disappeared and cell proliferation and viral replication ceased, but resumed following restimulation of rested cells with Ag or mAbs directed to CD3/CD28. In addition, higher cell death rates were observed in HIV-1-infected than uninfected cultures during secondary but not primary stimulation. Thus, this system may allow us to study the biology of HIV-1 latency, as well as the mechanisms of CD4+ T cell death following HIV-1 reactivation.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Address correspondence and reprint requests to Dr. Fabio Romerio, Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201. E-mail address: fromerio{at}ihv.umaryland.edu

2 Abbreviations used in this paper: HAART, highly active antiretroviral therapy; MDCC, monocyte-derived dendritic cell; 7AAD, 7-aminoactinomycin D; SEB, staphylococcal enterotoxin B; CHX, cycloheximide; AZT, azidothymidine; FCM, flow cytometry; TCM, central memory T; FSC-H, forward scatter height; SSC-H, side light scatter height.


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The JI 2008 181: 7433-7434. [Full Text]  






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