Cross-Reactive Anti-Nucleocapsid Protein Immunity against Crimean-Congo Hemorrhagic Fever Virus and Hazara Virus in Multiple Species

Abstract

The World Health Organization estimates that there may be three billion people at risk of infection by Crimean-Congo Hemorrhagic Fever Virus (CCHFV), a highly lethal, emerging orthonairovirus carried by ticks. On the other hand, the closely related Hazara virus (HAZV), a member of the same serogroup, has not been reported as a pathogen for humans. Given the structural and phylogenetic similarities between these two viruses, we evaluated the immunological similarities of the nucleocapsid protein (NP) of these two viruses in multiple species. Strong antigenic similarities were demonstrated in anti-NP humoral immune responses against HAZV and CCHFV in multiple species using convalescent human CCHF sera, rabbit and mouse polyclonal antiserum raised against CCHFV, and mouse polyclonal antiserum against CCHFV-NP in enzyme immunoassays. We also report a convincing cross-reactivity between NPs in Western blots using HAZV-infected cell lysate as antigen and inactivated CCHFV and CCHFV-NP-immunized mice sera. These results suggest that NPs of HAZV and CCHFV share significant similarities in humoral responses across species and underline the potential utility of HAZV as a surrogate model for CCHFV. IMPORTANCE CCHFV and HAZV, members of the Nairoviridae family, are transmitted to mammals by tick bites. CCHFV is considered to be a severe threat to public health and causes hemorrhagic diseases with a high mortality rate, and there are neither preventative nor therapeutic medications against CCHFV disease. HAZV, on the other hand, is not a pathogen to humans and can be studied under BSL-2 conditions. The antigenic relationship between these viruses is of interest for vaccines and for preventative investigations. Here, we demonstrate cross-reactivity in anti-NP humoral immune response between NPs of HAZV and CCHFV in multiple species. These results underline the utility of HAZV as a surrogate model to study CCHFV infection.

Immune responses in multiple hosts to Nucleocapsid Protein (NP) of Crimean-Congo Hemorrhagic Fever Virus (CCHFV)

“…Among the possible means by which virus infection could be constrained are the cytotoxic T cell activity and DTH type inflammatory responses. Together with the above-mentioned results and other previous studies, it could be stated that there is a strong NP-specific antibody response during the natural course of infection [ 51 , 52 ], and CD4+ cell epitopes on NP are recognized in multispecies.…”

First evidence of Crimean‐Congo haemorrhagic fever virus circulation in Bosnia and Herzegovina

“…This observation coincides with a recent study of age dependent CCHFV seroprevalences in Mauritanian livestock (Schulz et al, 2021). The simple explanation of this phenomenon is faced in the possibility that older animals are exposed to CCHFV-infected competent vectors longer than younger animals, and thus becoming infected should not be neglected (Kalkan-Yazıcı et al, 2021). In case that such antibodies led to false-positive CCHFV test results, the distribution and prevalence of CCHFV could be rather overestimated, especially in regions where other Othonairoviruses are prevalent (Hartlaub et al, 2021).…”

Hantaviruses use the endogenous host factor P58IPK to combat the PKR antiviral response

“…We confirmed the cross reactivity of anti-CCHFV NP antibody with bacterially expressed and purified HZV NP ( Fig 1E ). These anti-CCHFV NP antibodies have been previously used for HZV NP studies [ 27 ]. The cross-reactive CCHFV antibodies were used because the antibodies for HZV NP are not commercially available.…”