Abstract

Susceptibility of human seminal vesicles to HIV-1 infection

C. Deléage¹, H. Denis¹, N. Rioux-Leclercq², A. Ruffault³, B. Jégou¹, N. Dejucq-Rainsford<sup>1

1</sup>INSERM U625, Rennes, France, ²Anathomo-pathology, Rennes University Hospital, Rennes, France, ³Retrovirology, Rennes University Hospital, Rennes, France

Background: Semen represents the main vector for HIV dissemination worldwide. Even when HAART achieves undetectable viral load in the blood, semen can still harbor replication competent virus. Therefore, it is essential to determine the origin of HIV in the seminal plasma and assess whether the male genital tract is responsible for local production. The seminal vesicles (SV) may represent an important contributor to HIV shedding in semen as their secretions represents 60% of the seminal fluid. This study is the first to investigate the ability of human SV to support HIV infection.
Methods: Normal human SV were obtained from HIV-negative men. An organotypic culture was developed and characterized by histological examination, MTT assay, in situ detection of cell specific markers as well as real time PCR quantification of cell specific mRNAs. Potential immune target cells were quantified and SV explants were exposed to R5 (SF-162) HIV-1 strains for 3h at 37°C. HIV infection was detected by RT activity measure in culture supernatants and HIV DNA quantification. The infectiosity of produced virions was evaluated on PBMC.
Results: Human SV in culture display preserved tissue architecture and maintenance of all cell types for 15 days. Potential immune target cells in this organ consist mainly of CD68+ myeloid cells, whilst very few CD4+ T lymphocytes are observed. Following exposure to HIV-1 R5, a 10 fold increase in HIV DNA was observed in the SV from 3 donors between day 7 and day 15. Increased RT activity was measured in the culture supernatants. Day 15 supernatants of HIV infected SV led to productive infection of PBMC.
Conclusions: We demonstrated for the first time that human seminal vesicles can support HIV infection in vitro and therefore could contribute virus to semen. The infection of seminal vesicles from asymptomatic HIV+ men is currently being investigated.