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

Abstract

1 the precise origins of the infected leukocytes and free viral particles contaminating the seminal plasma remain unclear. Phylogenetic studies have established that HIV in semen arises from local sources within the male genital tract and/or from passive diffusion via the blood 2-4 (previous references in Le Tortorec and Dejucq-Rainsford 5 ). The existence of productive sources in the male genital tract is further substantiated through observations of several differences between blood and semen, including i) detection of persistent infectious HIV in the semen of 5% to 30% of men with undetectable blood viral load receiving fully suppressive antiretroviral therapy [5][6][7][8][9] ; ii) higher viral load in semen in a subpopulation of treatment-naïve men 10 ; iii) different rates, kinetics of emergence, and diversity of drug-resistant strains 4,11,12 ; and iv) different ratio of infected versus noninfected leukocytes. 13At present, the nature of the sources of HIV in the male genital tract remains unclear. This knowledge is crucial to the understanding of the biology of HIV sexual transmission and to the design of targeted therapies for eradicating HIV from semen.Semen is composed of secretions and cells from the testes, epididymides, prostate, seminal vesicles, and bulbo urethral glands. Vasectomy has little effect on seminal shedding of HIV-1 RNA, 14 which suggests that the testes and epididymides are not the primary sources of HIV particles in semen. The seminal vesicles, the secretions of which represent more than 60% of the seminal fluid, could be an important source of seminal HIV. We recently demonstrated that the seminal vesicles of asymptomatic macaques are productively infected by simian immunodeficiency virus (SIV) in vivo and, together with the prostate, exhibit the highest level of infection among the male genital tract organs in this animal model. 15 To date, infection of human seminal vesicles by HIV has not been reported.

Detection of Simian Immunodeficiency Virus in Semen, Urethra, and Male Reproductive Organs during Efficient Highly Active Antiretroviral Therapy

“…We previously demonstrated in both men and therapy-naive macaques the infection of T lymphocytes and macrophages in the epididymis, prostate, seminal vesicles, and testis using in situ hybridization combined with immunostaining (43,45,47,54,100).…”

“…Infected T lymphocytes predominated in the prostate (100), whereas infected macrophages were encountered primarily in the epididymis, seminal vesicle, and testis, together with some infected T lymphocytes (43,45,47). Such infected cells were no longer detected in these organs after 4 months of HAART in macaques.…”

“…Alexa-633, Alexa-594, or biotin-conjugated secondary antibodies were purchased from Invitrogen and Dako. Immunohistochemistry was performed as previously described (43). No staining was ever observed with isotype control antibodies.…”

“…ϩ T cells present in semen-producing organs (testis, epididymis, prostate, seminal vesicle) of therapy-naive men and macaques during the chronic stage are infected by HIV/SIV and may efficiently seed the semen with free viral particles and infected cells (43,(45)(46)(47)(48)100). Therefore, viral persistence in the semen may be attributable to viral production within the MGT organs, either because of incomplete penetration of antiretroviral drugs and/or because of the infection of long-lived cells in those tissues.…”

Human Male Genital Tract Immunity

“…These contain a secretory mucosa lined by a pseudostratified epithelium. There are numerous macrophages and, to a lesser extent, T lymphocytes (both CD4 and CD8) in the seminal vesicle epithelium, and this tissue is infectable in vivo and in vitro with HIV-1 (Deleage et al, 2011).…”