Human seminal plasma abrogates the capture and transmission of human immunodeficiency virus type 1 to CD4+ T cells mediated by DC-SIGN.
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 (1:10(4) to 1:10(5)), 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.
Sabatté
Juan
J
National Reference Center for AIDS, Department of Microbiology, Buenos Aires University School of Medicine, Argentina.
Ceballos
Ana
A
Raiden
Silvina
S
Vermeulen
Mónica
M
Nahmod
Karen
K
Maggini
Julián
J
Salamone
Gabriela
G
Salomón
Horacio
H
Amigorena
Sebastian
S
Geffner
Jorge
J
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism / Q000821:virology*; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012661:Semen / Q000502:physiology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D015699:HIV Envelope Protein gp120; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin