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REVIEW article

Front. Immunol.

Sec. Molecular Innate Immunity

Venturing into host-pathogen interaction in Crimean-Congo Hemorrhagic Fever (CCHF) to highlight Terra incognita

  • 1. Clinical Immunology Division, Institut National de Recherche Biomedicale, Kinshasa, Democratic Republic of Congo

  • 2. Microbiology Service, Department of Medical Biology, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo

  • 3. Ridgeback Biotherapeutics LP, Miami, United States

  • 4. Axis of Molecular Immunology and Pathogenesis, Molecular Biology Service, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo

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Abstract

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.

Summary

Keywords

antiviral, Crimean-Congo hemorrhagic fever, host, Immunity, Infection, virus

Received

30 October 2025

Accepted

16 February 2026

Copyright

© 2026 Shamamba, Mulangu and Kasumba. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Dacquin Muhandwa Kasumba

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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