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 medical countermeasures approved 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 the identification of a new variant with enough genetic divergence to require the creation of a second genotype. Although this variant HeV has produced fatal equine disease, its pathogenesis and lethality are unknown in humans. In the present study, we investigated the pathogenicity 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. Experimental challenge of AGMs with 5.0E5 PFU of 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 until the predetermined scientific endpoint of the study. 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 animal model and suggests that HeV-g2 may be less pathogenic in humans.