title: Susceptibility of human testis to human immunodeficiency virus-1 infection in situ and in vitro.
abstract: Semen represents the main vector for human immunodeficiency virus (HIV) dissemination worldwide and has been shown to harbor replication-competent virus despite otherwise effective highly active anti-retroviral therapy, which achieves undetectable viral load in plasma. Despite this, the origin of seminal HIV particles remains unclear, as does the question of whether the male genital tract organs contribute virus to semen. Here we investigated the presence of HIV receptors within the human testis using immunohistochemistry and quantitative real-time polymerase chain reaction. We also analyzed the infectivity of a dual tropic HIV-1 strain in an organotypic culture, as well as the impact of viral exposure on testosterone production. Our study establishes that CXCR4+, CCR5+, CD4+, and DC-SIGN+ cells are present within the interstitial tissue of human testis and that these molecules persist throughout our organotypic culture. Our data also reveal that the human testis is permissive to HIV-1 and supports productive infection, leaving testosterone production apparently unaffected. Infected cells appeared to be testicular macrophages located within the interstitial tissue. That the testis itself represents a potential source of virus in semen could play a role in preventing viral eradication from semen because this organ constitutes a pharmacological sanctuary for many current antiretrovirals.
authors.affiliation: INSERM U625-GERHM, Campus Scientifique de Beaulieu, Avenue du Général Leclerc, 35 042 Rennes Cedex, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roulet
authors.forename: Anne-Pascale
authors.initials: AP
authors.lastname: Satie
authors.forename: Annick
authors.initials: A
authors.lastname: Ruffault
authors.forename: Anna
authors.initials: A
authors.lastname: Le Tortorec
authors.forename: Hélène
authors.initials: H
authors.lastname: Denis
authors.forename: Odile
authors.initials: O
authors.lastname: Guist'hau
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Patard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclerq
authors.forename: Janine
authors.initials: J
authors.lastname: Gicquel
authors.forename: Bernard
authors.initials: B
authors.lastname: Jégou
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dejucq-Rainsford
mesh_terms: D004279:DNA, Viral / Q000378:metabolism*; D004198:Disease Susceptibility; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D009924:Organ Culture Techniques; D012367:RNA, Viral / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D013997:Time Factors
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D015728:Receptors, HIV