Characterization of a Novel STAT 2 Knock Out Hamster Model of Crimean Congo Hemorrhagic Fever Virus Pathogenesis

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen causing a febrile illness in humans, which can progress to hemorrhagic manifestations, multi-organ failure, and death. Current mouse models of CCHFV infection reliably succumb to virus challenge but vary in their ability to reflect signs of disease similar to humans. In this study, we established a signal transducer and activator of transcription 2 (STAT2) knockout hamster model to expand the repertoire of animal models of CCHFV pathogenesis that can be used for therapeutic development. These hamsters demonstrated a systemic and lethal disease in response to infection. Hallmarks of human disease were observed including petechial rash, blood coagulation dysfunction, and various biochemistry and blood cell count abnormalities. Furthermore, we also demonstrated the utility of this model for anti-CCHFV therapeutic evaluation. The STAT2 knock-out hamster model of CCHFV infection may provide some further insights into clinical disease, viral pathogenesis, and pave the way for testing of potential drug and vaccine candidates

A simple protein-based surrogate neutralization assay for SARS-CoV-2

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector–based assay