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Journal of Virology, December 2007, p. 13723-13734, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01079-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human Seminal Plasma Abrogates the Capture and Transmission of Human Immunodeficiency Virus Type 1 to CD4+ T Cells Mediated by DC-SIGN{triangledown}

Juan Sabatté,1 Ana Ceballos,1 Silvina Raiden,2 Mónica Vermeulen,2 Karen Nahmod,2 Julián Maggini,2 Gabriela Salamone,2 Horacio Salomón,1 Sebastian Amigorena,3 and Jorge Geffner1,2*

National Reference Center for AIDS, Department of Microbiology, Buenos Aires University School of Medicine,1 Institute of Hematologic Research, National Academy of Medicine, Buenos Aires, Argentina,2 Institut National de la Sante et de la Recherche Medicale U365, Immunite et Cancer, Institut Curie, Paris, France3

Received 18 May 2007/ Accepted 24 September 2007

Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is expressed by dendritic cells (DCs) at mucosal surfaces and appears to play an important role in the dissemination of human immunodeficiency virus type 1 (HIV-1) infection. DC-SIGN binds HIV-1 gp120 and efficiently transmits the virus to T CD4+ cells, which become the center of viral replication. Semen represents the main vector for HIV-1 dissemination worldwide. In the present study we show that human seminal plasma (SP), even when used at very high dilutions (1:104 to 1:105), markedly inhibits the capture and transmission of HIV-1 to T CD4+ cells mediated by both DCs and B-THP-1-DC-SIGN cells. In contrast, SP does not inhibit the capture of HIV-1 by DC-SIGN-negative target cells, such as the T-cell line SupT-1, monocytes, and activated peripheral blood mononuclear cells. The SP inhibitor has a high molecular mass (>100 kDa) and directly interacts with DC-SIGN-positive target cells but not with HIV-1. Moreover, the inhibitor binds to concanavalin A, suggesting that it contains high-mannose N-linked carbohydrates. Of note, using biotin-labeled SP we found that the binding of SP components to DCs was abrogated by mannan, while their interaction with B-THP-1 cells was almost completely dependent on the expression of DC-SIGN. Since epithelium integrity is often compromised after vaginal or anal intercourse, as well as in the presence of ulcerative-sexually transmitted diseases, our results support the notion that components of the SP might be able to access to the subepithelium, inhibiting the recognition of HIV-1 gp120 by DC-SIGN-positive DCs.

* Corresponding author. Mailing address: Departamento de Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. Phone: 5411-48055695. Fax: 5411-48039475. E-mail: geffnerj{at}fibertel.com.ar

{triangledown} Published ahead of print on 3 October 2007.

Journal of Virology, December 2007, p. 13723-13734, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01079-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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