title: Semen CD4+ T cells and macrophages are productively infected at all stages of SIV infection in macaques.
abstract: The mucosal events of HIV transmission have been extensively studied, but the role of infected cells present in the genital and rectal secretions, and in the semen, in particular, remains a matter of debate. As a prerequisite to a thorough in vivo investigation of the early transmission events through infected cells, we characterized in detail by multi-parameter flow cytometry the changes in macaque seminal leukocytes during SIVmac251 infection, focusing on T cells, macrophages and dendritic cells. Using immunocytofluorescence targeting SIV proteins and real-time quantitative PCR targeting SIV DNA, we investigated the nature of the infected cells on sorted semen leukocytes from macaques at different stages of infection. Finally, we cocultured semen CD4(+) T cells and macrophages with a cell line permissive to SIV infection to assess their infectivity in vitro. We found that primary infection induced strong local inflammation, which was associated with an increase in the number of leukocytes in semen, both factors having the potential to favor cell-associated virus transmission. Semen CD4(+) T cells and macrophages were productively infected at all stages of infection and were infectious in vitro. Lymphocytes had a mucosal phenotype and expressed activation (CD69 & HLA-DR) and migration (CCR5, CXCR4, LFA-1) markers. CD69 expression was increased in semen T cells by SIV infection, at all stages of infection. Macrophages predominated at all stages and expressed CD4, CCR5, MAC-1 and LFA-1. Altogether, we demonstrated that semen contains the two major SIV-target cells (CD4+ T cells and macrophages). Both cell types can be productively infected at all stages of SIV infection and are endowed with markers that may facilitate transmission of infection during sexual exposure.
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Bernard-Stoecklin
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Gommet
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Aurélien B
authors.initials: AB
authors.lastname: Corneau
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Guenounou
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Torres
authors.affiliation: INSERM U1085-IRSET, Université de Rennes 1, Structure Fédérative Recherche Biosit, Campus de Beaulieu, Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dejucq-Rainsford
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cosma
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.affiliation: CEA, Division of Immuno-Virology, iMETI/DSV, Fontenay-aux-Roses, France ; UMR-E1, Université Paris Sud 11, Orsay, France ; Vaccine Research Institute (VRI), Créteil, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D008252:Macaca fascicularis; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D008297:Male; D010641:Phenotype; D012661:Semen / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D017201:Virus Shedding
chemical_list: D004279:DNA, Viral