Venturing into host-pathogen interaction in Crimean-Congo hemorrhagic fever to highlight terra incognita.

Crimean-Congo- Hemorrhagic Fever (CCHF) is the most widespread tick-borne disease in the world with a highly variable case fatality rate. It is caused by the CCHF virus (CCHFV). The disease, which has neither approved treatments nor vaccines, has long received very little attention until it was listed as a priority pathogen by WHO. Improving our understanding of mechanisms of host-virus interaction is essential for the development of effective therapeutic and prophylactic strategies. There is still much to be clarified to better understand how the virus interacts with its host and humans. Elucidating these mechanisms will provide insights into viral pathogenesis, immune evasion strategies, and host defense responses. As a result, this will stimulate the development of targeted interventions to mitigate disease severity and improve clinical outcomes. Better understanding of virus characteristics will also improve our surveillance capability which is critical for developing effective pandemic preparedness and outbreak response strategies. Here, we examine the existing landscape concerning the immune response and inflammatory events in CCHFV-human interaction and discuss gaps in our understanding of the disease. Such discussions allow us to highlight priority research directions for the identification of potential targets for improved mitigation approaches or specific therapeutic routes.