This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Frank, I. Articles by Robbiani, M. Search for Related Content PubMed PubMed Citation Articles by Frank, I. Articles by Robbiani, M.

 Previous Article  |  Next Article 

Journal of Virology, June 2008, p. 5329-5339, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.01987-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Fusion Inhibitor Prevents Spread of Immunodeficiency Viruses, but Not Activation of Virus-Specific T Cells, by Dendritic Cells

I. Frank,¹ H. Stössel,² A. Gettie,³ S. G. Turville,^1, J. W. Bess Jr.,⁴ J. D. Lifson,⁴ I. Sivin,¹ N. Romani,² and M. Robbiani^1*

Center for Biomedical Research, Population Council, New York, New York 10065,¹ Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria,² Aaron Diamond AIDS Research Center, 455 First Avenue New York, New York 10016,³ AIDS Vaccine Program, SAIC Frederick, National Cancer Institute at Frederick, Building 535, Frederick, Maryland 21702⁴

Received 10 September 2007/ Accepted 14 March 2008

Dendritic cells (DCs) play a key role in innate immune responses, and their interactions with T cells are critical for the induction of adaptive immunity. However, immunodeficiency viruses are efficiently captured by DCs and can be transmitted to and amplified in CD4⁺ T cells, with potentially deleterious effects on the induction of immune responses. In DC-T-cell cocultures, contact with CD4⁺, not CD8⁺, T cells preferentially facilitated virus movement to and release at immature and mature DC-T-cell contact sites. This occurred within 5 min of DC-T-cell contact. While the fusion inhibitor T-1249 did not prevent virus capture by DCs or the release of viruses at the DC-T-cell contact points, it readily blocked virus transfer to and amplification in CD4⁺ T cells. Higher doses of T-1249 were needed to block the more robust replication driven by mature DCs. Virus accumulated in DCs within T-1249-treated cocultures but these DCs were actually less infectious than DCs isolated from untreated cocultures. Importantly, T-1249 did not interfere with the stimulation of virus-specific CD4⁺ and CD8⁺ T-cell responses when present during virus-loading of DCs or for the time of the DC-T-cell coculture. These results provide clues to identifying strategies to prevent DC-driven virus amplification in CD4⁺ T cells while maintaining virus-specific immunity, an objective critical in the development of microbicides and therapeutic vaccines.

---

* Corresponding author. Mailing address: Center for Biomedical Research, HIV and AIDS Program, Population Council, 1230 York Avenue, New York, NY 10065. Phone: (212) 327-7794. Fax: (212) 327-7764. E-mail: mrobbiani{at}popcouncil.org

Published ahead of print on 26 March 2008.

Present address: Center for Virus Research, Westmead Millennium Institute, Westmead Hospital and University of Sydney, Sydney, NSW 2145, Australia.

---

Journal of Virology, June 2008, p. 5329-5339, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.01987-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Trapp, S., Derby, N. R., Singer, R., Shaw, A., Williams, V. G., Turville, S. G., Bess, J. W. Jr., Lifson, J. D., Robbiani, M. (2009). Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G. J. Virol. 83: 884-895 [Abstract] [Full Text]