Crimean-Congo Hemorrhagic Fever Virus Localization and Shedding in the Reproductive Tract of Lethal and Survivor Mouse Models

Hemorrhagic fever viruses have been shown to localize to immune-privileged sites, including the reproductive tract, raising important questions about long-term persistence and the potential for sexual transmission. Anecdotal evidence of sexual transmission of Crimean-Congo hemorrhagic fever virus (CCHFV) has been reported, and <i>in vivo</i> studies suggest that CCHFV can localize to reproductive tissues; however, to date, this phenomenon has not been explicitly investigated. We evaluated histopathology and viral loads (viral RNA, viral antigen, and infectious viral titers) in reproductive tissues obtained from lethal and survivor mouse models of CCHFV during acute and convalescent phases of infection. Viral loads in urogenital swabs were also evaluated to assess the potential for virus transmission. Although no evidence of long-term persistence was observed in the survivor model of CCHF, our data indicate a potential for sexual transmission during acute infection, even in cases of mild disease, as infectious virus was isolated from urogenital swabs. These data support the importance of sampling human patients to better define the risk of sexual transmission and potential viral persistence in reproductive tissues during and after recovery from CCHF.