Experimental challenge of African green monkeys with contemporary Hendra virus isolates produces divergent clinical disease

Hendra virus (HeV) is a medically important, zoonotic paramyxovirus that emerged over thirty years ago which causes severe, often fatal disease in humans and animals. There are presently no approved medical countermeasures to prevent or treat human HeV disease, although many are in various stages of development. Critical to the stringent evaluation of these experimental countermeasures are nonhuman primate models of HeV disease which accurately recapitulate the pathogenesis of human infection. The continued emergence of HeV since its initial discovery in 1994 has recently expanded to include a second genotype. Although this variant HeV produced fatal equine disease, its pathogenesis and lethality are unknown in humans. Here, we investigated the pathogenesis of clinically relevant and contemporary HeV isolates from genotype 1 (HeV/Australia/Horse/2008/Redlands) and genotype 2 (HeV-var/Australia/Horse/2015/Gympie) in the African green monkey (AGM) model of henipavirus disease. AGMs challenged with HeV genotype 1 (HeV-g1) or genotype 2 (HeV-g2) isolates via the combined intranasal/intratracheal route of exposure produced divergent survival outcomes, with four of five AGMs infected with the HeV-g2 isolate surviving. All five HeV-g1 infected subjects developed acute HeV disease which accurately recapitulated HeV pathogenesis reported in humans. Our findings revealed that HeV-g2 is less pathogenic than HeV-g1 in the AGM model and suggests that HeV-g2 may be less pathogenic in humans.