Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells.
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.
Centro Nacional de Referencia para SIDA, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina.
Ana
A
Ceballos
Federico
F
Remes Lenicov
Juan
J
Sabatté
Christian
C
Rodríguez Rodrígues
Mercedes
M
Cabrini
Carolina
C
Jancic
Silvina
S
Raiden
Mónica
M
Donaldson
Rodolfo
R
Agustín Pasqualini
Clara
C
Marin-Briggiler
Mónica
M
Vazquez-Levin
Francisco
F
Capani
Sebastián
S
Amigorena
Jorge
J
Geffner
D000328:Adult; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006497:Heparan Sulfate / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012661:Semen / Q000276:immunology / Q000821:virology; D013094:Spermatozoa / Q000276:immunology* / Q000821:virology*; D053585:Virus Attachment
D006497:Heparan Sulfate; D016753:Interleukin-10; D018664:Interleukin-12; C508609:IL10 protein, human