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Journal of Virology, November 2002, p. 10692-10701, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10692-10701.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Dendritic Cell-Mediated Viral Transfer to T Cells Is Required for Human Immunodeficiency Virus Type 1 Persistence in the Face of Rapid Cell Turnover

Suryaram Gummuluru,1 Vineet N. KewalRamani,2 and Michael Emerman1*

Divisions of Human Biology and Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 217022

Received 5 April 2002/ Accepted 26 July 2002

Human immunodeficiency virus type 1 (HIV-1)-infected and activated CD4+ T cells have short half-lives in vivo (<2 days). We have established an in vitro culture system in which infected T cells are turned over frequently to provide a model system that examines this important facet of in vivo HIV-1 replication. We observed that virus replication in T cells under rapid-turnover conditions was possible only when immature dendritic cells or DC-SIGN-expressing cells mediated HIV-1 transmission to T cells. Virus replication was initiated more rapidly in T cells infected with the cell-associated form of virus compared to infection by the cell-free route. This accelerated transfer of virus required adhesion molecule-mediated interactions between the virus-presenting cell and T cell, but surprisingly, HIV-1 transfer could occur independently of DC-SIGN (DC-specific intracellular adhesion molecule 3 [ICAM-3]-grabbing nonintegrin)in the dendritic-cell-T-cell cocultures. These results suggest that dendritic cell-mediated transmission of HIV-1 enables virus replication under conditions of rapid cell turnover in vivo.

* Corresponding author. Mailing address: Divisions of Human Biology and Basic Sciences, Mailstop C2-023, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, P.O. Box 19024, Seattle, WA 98109. Phone: (206) 667-5058. Fax: (206) 667-6523. E-mail: memerman{at}fhcrc.org.

Journal of Virology, November 2002, p. 10692-10701, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10692-10701.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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