Persistence and Local Maintenance of STLV-1 Infection in the Vaginal Epithelium of Postmenopausal Japanese Macaques

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) and simian T-cell leukemia virus type 1 (STLV-1) primarily infect CD4+ T-cells and spread via cell-to-cell contact in vivo. However, the mechanism underlying viral establishment and persistence in local tissues remain poorly understood. From the perspective of sexually transmitted infections, this study aimed to visualize the infection status of the genital epithelium in relation to sexual STLV-1 infection before and after menopause. METHODS: In this study, we evaluated viral localization in the genital epithelium of naturally infected female Japanese macaques with STLV-1, which is highly homologous to HTLV-1. RESULTS: A marked increase in the proviral load (PVL) of STLV-1 was observed in both the vaginal epithelium and peripheral blood in post-compared with premenopausal individuals. Immunostaining showed the expression of glucose transporter 1 (GLUT1), a receptor for HTLV-1, in the basal layer of the vaginal epithelium. Additionally, in situ hybridization revealed strong expression of the viral accessory factor SBZ, the STLV-1 homolog of HBZ, relative to the pX region, which contains the Tax and Rex genes within the vaginal epithelium, indicating its involvement in latent infections at that site. In postmenopausal macaques, thinning of the vaginal epithelium was observed in association with decreased estradiol levels. Furthermore, more diverse and unique clones were identified in the vaginal epithelium of postmenopausal macaques than in peripheral blood mononuclear cells. CONCLUSIONS: These findings highlight the vaginal epithelium may serve as a site for the maintenance of persistent and de novo STLV-1 infections within the genital tract.