Pathogenesis of Chapare virus in cynomolgus macaques

Chapare virus (CHAPV) is an emerging New World arenavirus that is the causative agent of Chapare haemorrhagic fever (CHHF) responsible for recent outbreaks with alarmingly high case fatality rates in Bolivia near the Brazilian border. Here, we describe a nonhuman primate (NHP) model of CHHF infection which represents an essential tool to understand this emerging biological threat agent. Cynomolgus macaques challenged intravenously with CHAPV develop clinical disease, which recapitulates several key features of human CHHF. All subjects lost weight and had clinical scores following the CHAPV challenge. Notably, one of four NHPs developed a lethal disease with viral hepatitis and haemorrhagic features. Clinical chemistry and haematology revealed leukopoenia, anaemia, thrombocytopenia, and increased transaminase levels. In all four subjects, viremia was detectable for the first week following the challenge and viral RNA was detectable in serum and many tissues persisting 35 days post-challenge. Several medical countermeasures (MCM) have efficacy against CHAPV infection <i>in vitro</i>, but the current model for MCM testing and approval of new drugs is reliant on the availability of animal models. This work lays the foundation for future CHHF MCM development.