Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

Zivcec, Marko; Scholte, Florine E. M.; Spiropoulou, Christina F.; Spengler, Jessica R.; Bergeron, Éric

Existing interferon-α/β receptor (IFNAR)´/´and STAT1´/´mouse models of CCHF have been used to screen the efficacy of antivirals [119, 120] and experimental vaccines [121] [122] [123] [124] . The development of the existing disease models and studies of CCHFV-infected cells indicate the importance of the early innate immune response in disease [88, 125] . In order to better model early events in human infection, continued efforts should be made in the development of immunocompetent CCHF animal models. An immunocompetent model may provide critical insight into correlates of protection and enhance our understanding of the molecular mechanisms underlying pathogenesis that are largely restricted to in vitro investigations at this time. Given the complex role of the immune response in CCHF pathogenesis, such models would be invaluable for screening new therapeutic and vaccine candidates. CCHFV has been recognized as a significant emerging public health threat and is becoming a higher public health priority. Vaccine and therapeutic development for CCHF are rapidly expanding fields. However, a summary of these fields is beyond the scope of this review. Here we review recent in vitro experimental research efforts aimed at elucidating the mechanisms of CCHFV replication and pathogenesis. We provide a comprehensive summary of the known aspects of the CCHFV replication cycle, viral protein function, and cell-mediated host responses to infection. We also identify areas in CCHFV research that remain unknown or unclear, and merit additional investigation.