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(American Journal of Pathology. 2006;169:2094-2103.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060191

Susceptibility of Human Testis to Human Immunodeficiency Virus-1 Infection in Situ and in Vitro

Vanessa Roulet*, Anne-Pascale Satie*, Annick Ruffault{dagger}, Anna Le Tortorec*, Hélène Denis*, Odile Guist’hau{dagger}, Jean-Jacques Patard{ddagger}, Nathalie Rioux-Leclerq§, Janine Gicquel{dagger}, Bernard Jégou* and Nathalie Dejucq-Rainsford*

From INSERM U625,* Rennes; University of Rennes I, Groupe d’Etude de la Reproduction chez l’Homme et les Mammifères, IFR 140, Campus de Beaulieu, Rennes; and the Unité de Rétrovirologie{dagger} and Services d’Urologie{ddagger} and d’Anatomo-Pathologie,§ Centre Hospitalier Universitaire Régional Pontchaillou, Rennes, France

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 pro-ductive 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 anti-retrovirals.




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Copyright © 2006 by the American Society for Investigative Pathology.