Crimean-Congo Hemorrhagic Fever Virus localization and shedding in the reproductive tract of lethal and survivor mouse models

Authors: SORVILLO, TERESA - Centers For Disease Control And Prevention (CDC) - United States; RITTER, JANA - Centers For Disease Control And Prevention (CDC) - United States; WELCH, STEPHEN - Centers For Disease Control And Prevention (CDC) - United States; DAVIES, KATHERINE - Oak Ridge Institute For Science And Education (ORISE); COLEMAN-MCCRAY, JOANN - Centers For Disease Control And Prevention (CDC) - United States; HAYES, HEATHER - Centers For Disease Control And Prevention (CDC) - United States; FICARRA, G - Centers For Disease Control And Prevention (CDC) - United States; BHATNAGER, J - Centers For Disease Control And Prevention (CDC) - United States; SPIROPOULOU, CHRISTINA - Centers For Disease Control And Prevention (CDC) - United States; SPENGLER, JESSICA - Centers For Disease Control And Prevention (CDC) - United States; PEGAN, SCOTT - University Of California; BERGERON, ERIC - Centers For Disease Control And Prevention (CDC) - United States; MONTGOMERY, JOEL - Centers For Disease Control And Prevention (CDC) - United States

Submitted to: Emerging Microbes & Infections
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2025
Publication Date: 11/27/2025
Citation: Sorvillo, T.E., Ritter, J.M., Welch, S.R., Davies, K.A., Coleman-Mccray, J.D., Hayes, H.M., Ficarra, G., Bhatnager, J., Spiropoulou, C.F., Spengler, J.R., Pegan, S.D., Bergeron, E., Montgomery, J.M. 2025. Crimean-Congo Hemorrhagic Fever Virus localization and shedding in the reproductive tract of lethal and survivor mouse models. Emerging Microbes & Infections. 15. https://doi.org/10.1080/22221751.2025.2595795.
DOI: https://doi.org/10.1080/22221751.2025.2595795

Interpretive Summary: The question of if CCHFV can persist, or be shed from reproductive tissues has been largely unstudied and remains an important question to assess if viral persistence may permit sexual transmission. By using lethal and survivor models of CCHFV in transiently immunosupressed mice, viral loads (viral RNA and infectious virus) were quantified in reproductive tissues and from urogenital swabs. This revealed that both vRNA and infectious virus could be detected in specimens taken during acute infection, even when disease presentation was mild. This finding suggests a plausible window for sexual transmission of CCHFV, and highlight the need for assessment of viral persistence in humans, both during acute cases and in survivors, to further understand risks.

Technical Abstract: 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 in vivo 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.