Testicular germ cells of HIV-seropositive asymptomatic men are infected by the virus

Abstract

In situ PCR hybridization studies in the testis of infected asymptomatic subjects detected the presence of HIV-1 proviral DNA in the nuclei of germ cells at all stages of differentiation suggesting that HIV-seropositive men produce infected spermatozoa that are released in the genital tract. In all subjects studied spermatogenesis was normal, the presence of provirus was not associated with germ cell damage and a very mild local immune response was observed. The HIV hybridization pattern observed in germ cells supports the hypothesis of a clonal infection. It is suggested the possibility of a direct infection of the germ cells by cell-free virus and that the testis might represent a site of early viral localization, well tolerated because of the immune privilege of this organ.

Introduction

It is well known that, during HIV infection, testes undergo a series of pathologic changes, which eventually lead to arrest of spermatogenesis, interstitial fibrosis and irreversible testicular atrophy (Chabon et al., 1987, De Paepe and Waxman, 1989, Dalton and Harcourt-Webster, 1991). Pathogenic mechanisms responsible for these events have not been clarified and most of the observations on the presence and cellular distribution of the virus in the testis have been performed on autopsy material from men dying from AIDS (Lecatsas et al., 1985, Da Silva et al., 1990, Pudney and Anderson, 1991, Nuovo et al., 1994). Information from subjects at early stages of the disease could contribute to a better understanding of testicular pathology in HIV-infected men.

In addition, it has to be considered that the testis is an immunologically privileged site of the body (Dym and Fawcett, 1970, Tung, 1980), where germ cell-linked autoantigens, that elicit strong autoimmune reactions if injected elsewhere (De Cesaris et al., 1992), are physiologically tolerated. The testis immune privilege appears to be regulated by a series of cellular and molecular mechanisms (Dym and Fawcett, 1970, Tung, 1980, Jackson et al., 1991, De Cesaris et al., 1992, Gray et al., 1992, Bellgrau et al., 1995, Sanberg et al., 1996). The testis could, therefore, represent an early and well tolerated site of HIV localization and/or replication and a precocious route for virus diffusion into the genital ducts.

We have recently studied, by in situ PCR hybridization, the presence and cellular distribution of HIV-1 proviral DNA in testes of HIV-infected men at various stages of the disease (Muciaccia et al., 1998). In this paper, we examine testes in the early stages of the disease, obtained from HIV-seropositive asymptomatic men.