Search

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-phase 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 mouse 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 Crimean-Congo hemorrhagic fever virus (CCHFV) and Hazara virus (HAZV), members of the Nairoviridae family, are transmitted to mammals by tick bites. CCHFV is considered 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 biosafety level 2 (BSL2) conditions. The antigenic relationship between these viruses is of interest for vaccines and for preventative investigations. Here, we demonstrate cross-reactivity in anti-nucleocapsid protein (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.

The recent pandemic of COVID-19 has caused a tremendous alarm around the world. Details of the infection process in the host have significant bearings on both recovery from the disease and on the correlates of the protection from the future exposures. One of these factors is the presence and titers of neutralizing Abs (NAbs) in infected people. In the current study, we set out to investigate NAbs in the recovered subjects discharged from the hospital in full health. Serum samples from a total of 49 documented consecutive COVID-19 subjects were included in the study. All the subjects were adults, and serum samples collected during the discharge were tested in viral neutralization, enzyme immunoassay (EIA), and Western immunoblot tests against viral Ags. Even though a majority of the recovered subjects had raised significant NAb titers, there is a substantial number of recovered patients (10 out of 49) with no or low titers of NAbs against the virus. In these cohorts as well as in patients with high NAb titers, viral Ag binding Abs were detectable in EIA tests. Both NAb titers and EIA detectable Abs are increased in patients experiencing a severe form of the disease, and in older patients the Ab titers were heightened. The main conclusion is that the recovery from SARS-CoV-2 infection is not solely dependent on high NAb titers in affected subjects, and this recovery process is probably produced by a complex interplay between many factors, including immune response, age of the subjects, and viral pathology.

Hazara virus (HAZV), a tick-borne agent of the nairoviruses, is closely related to Crimean–Congo hemorrhagic fever virus (CCHFV). Hazara virus has not been reported as a pathogen for humans and can be studied under BSL-2 conditions, whereas CCHFV causes severe hemorrhagic diseases, with up to 30% mortality rate in humans, and requires BSL-4 facilities to be handled. Serologic and phylogenetic similarities between the two viruses would therefore be an interesting area of research. In this study, we evaluated the immunological similarities between these two viruses using nucleocapsid protein as a model. Here, we evaluated cross-reactivity between CCHFV and HAZV rNP, which forms virus-like particles when expressed in Pichia pastoris. In Western blot assays using CCHFV-infected human and immunized mice and rabbit sera, cross-reactions were detected between the nucleoproteins of both viruses. Virus-like particles were visualized by transmission electron microscopy (TEM) and monitored by dynamic light scattering (DLS). These results suggest that nucleocapsid proteins of HAZV and CCHFV share similarities regarding the antiviral humoral response in both species.