A recombinant Cedar virus preclinical model that recapitulates neurological features of henipavirus disease

Nipah virus (NiV) and Hendra virus (HeV) are members of the henipavirus genus that cause severe respiratory and/or neurological disease in humans. Because NiV and HeV can only be handled under BSL-4 containment, there are significant practical barriers to the study of pathogenicity and the evaluation of therapeutic countermeasures. However, Cedar virus (CedV) is a non-pathogenic henipavirus that can be used in a BSL-2 setting. Here, we demonstrate that recombinant CedVs that express the F and G glycoproteins of NiV or HeV display an in vivo tissue tropism that better emulates authentic NiV and HeV. Moreover, by severely impairing interferon signaling through the use of STAT1-deficient mice, we show that rCedVs expressing NiV/HeV F and G cause neurological disease signs and mortality in most animals. Thus, this BSL-2 mouse model represents a powerful tool for pre-clinical investigation of candidate therapeutics and studies of henipavirus pathogenesis mechanisms.