The Role of Nucleocapsid Protein (NP) in the Immunology of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

Crimean-Congo hemorrhagic fever virus (CCHFV) is an orthonairovirus from the Bunyavirales order that is widely distributed geographically and causes severe or fatal infections in humans. The viral genome consists of three segmented negative-sense RNA molecules. The CCHFV nucleocapsid protein (CCHFV NP) is encoded by the smallest segment of the virus. CCHFV NP, the primary function of which is the encapsidation of viral RNA molecules, plays a critical role in various mechanisms important for viral replication and pathogenesis. This review is an attempt to revisit the literature available on the highly immunogenic and highly conserved CCHFV NP, summarizing the multifunctional roles of this protein in the immunology of CCHFV. Specifically, the review addresses the impact of CCHFV NP on innate, humoral, and cellular immune responses, epitopes recognized by B and T cells that limit viral spread, and its role as a target for diagnostic tests and for vaccine design. Based on the extensive information generated by many research groups, it could be stated that NP constitutes a significant and critical player in the immunology of CCHFV.