Animal Models for Henipavirus Research

Hendra virus (HeV) and Nipah virus (NiV) are zoonotic paramyxoviruses in the genus Henipavirus (HNV) that emerged nearly thirty years ago. Outbreaks of HeV and NiV have led to severe respiratory disease and encephalitis in humans and animals characterized by a high mortality rate. Despite the grave threat HNVs pose to public health and global biosecurity, no approved medical countermeasures for human use currently exist against HeV or NiV. To develop candidate vaccines and therapeutics and advance the field's understanding of HNV pathogenesis, animal models of HeV and NiV have been instrumental and remain indispensable. Various species, including rodents, ferrets, and nonhuman primates (NHPs), have been employed for HNV investigations. Among these, NHPs have demonstrated the closest resemblance to human HNV disease, although other animal models replicate some key disease features. Here, we provide a comprehensive review of the currently available animal models (mice, hamsters, guinea pigs, ferrets, cats, dogs, nonhuman primates, horses, and swine) to support HNV research. We also discuss the strengths and limitations of each model for conducting pathogenesis and transmission studies on HeV and NiV and for the evaluation of medical countermeasures.