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 With sexual contact being the main cause of the spread of human immunodeficiency virus (HIV) and male to female transmission rates being higher and more efficient than female to male, semen represents the foremost vector of HIV dissemination worldwide. However, the origin of the virus in the semen is still unclear. Several arguments point to the existence of local sources producing free viral particles in this bodily fluid. First, a number of studies clearly indicate that semen represents a viral compartment distinct from the blood.

Human Immunodeficiency Virus Infects Human Seminal Vesicles in Vitro and in Vivo

“…18 For infectivity assay, 500 L seminal vesicle culture supernatants collected at the day of peak reverse transcriptase activity or 500 L viral stock used for infection and maintained at 37°C for 9 days, used here as a negative control, was ultracentrifuged for 3 hours at 39,500 ϫ g. Supernatants were discarded, and the pellets were dissolved in 500 L RPMI 1640, which was added to 4 ϫ 10 6 phytohemagglutinin-activated PBMCs for 3 hours at 37°C. PBMCs were resuspended in 2 mL RPMI 1640 supplemented with 5% IL-2 and maintained at 37°C for 15 days.…”

“…18 In brief, after antigen retrieval [1 mmol/L EDTA (pH 9.0) or 10 mmol/L citrate (pH 6.0) for 20 minutes] and blockage of unspecific sites with 4% normal human serum in PBS, tissues were reacted at 4°C overnight using the appropriate antibody diluted in PBS containing 2% normal human serum. The primary antibody was replaced with the appropriate isotopic control at the same concentration in control sections.…”

“…Quantitative real-time PCR for HIV-1 LTR DNA and for the albumin gene used as a reference was performed on 250 ng DNA, as previously described. 18 For each donor and each time point, two separate blocks of tissue were analyzed in duplicate.…”

Le tractus génital masculin

“…Avant nos travaux, peu d'études avaient été effectuées sur l'infection du tractus génital masculin en raison de la difficulté d'accès aux organes génitaux d'hommes VIH + . Afin de pallier ce problème, notre équipe a développé une culture organotypique de tissu testiculaire [30] qui a permis de montrer que le testicule humain est infecté par le VIH-1 in vitro [31]. In vivo, l'infection de cet organe a été mise en évidence dans un modèle animal qui mime l'infection chez l'homme -les macaques cynomolgus infectés par le SIV (virus de l'immunodéficience simienne).…”

RNA interference and HIV‐1 infection

“…To date, complete viral clearance is quite hard to be achieved in patients with established HIV infection, in part because of hidden latent virion reservoirs in HIV permissive cells containing integrated and transcriptionally silent provirus [12][13][14].…”