Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells

CEBALLOS A; REMES LENICOV F; SABATTÉ J; RODRIGUEZ RODRIGUES C; CABRINI M; JANCIC C; RAIDEN S; DONALSON M; PASQUALINI RA; MARIN-BRIGGILER C; VEZQUEZ-LEVIN M; CAPANI F; AMIGORENA S; GEFFNER J

JOURNAL OF EXPERIMENTAL MEDICINE

ROCKEFELLER UNIV PRESS

Año: 2009 vol. 206 p. 2717 - 2733

0022-1007

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES;} @page Section1 {size:595.3pt 841.9pt; margin:42.55pt 42.55pt 42.55pt 42.55pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Semen is the main vector for HIV-1 dissemination worldwide. It contains three major sources of infectious virus: free virions, infected leukocytes, and spermatozoa-associated virions. We focused on the interaction of HIV-1 with human spermatozoa and dendritic cells (DCs). We report that heparan sulfate is expressed in spermatozoa and plays an important role in the capture of HIV-1. Spermatozoa-attached virus is efficiently transmitted to DCs, macrophages, and T cells. Interaction of spermatozoa with DCs not only leads to the transmission of HIV-1 and the internalization of the spermatozoa but also results in the phenotypic maturation of DCs and the production of IL-10 but not IL-12p70. At low values of extracellular pH (approximately 6.5 pH units), similar to those found in the vaginal mucosa after sexual intercourse, the binding of HIV-1 to the spermatozoa and the consequent transmission of HIV-1 to DCs were strongly enhanced. Our observations support the notion that far from being a passive carrier, spermatozoa acting in concert with DCs might affect the early course of sexual transmission of HIV-1 infection.