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

Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus that causes severe disease in humans and animals. While all confirmed human cases have been associated with genotype 1 (HeV-g1), a genetically distinct genotype 2 (HeV-g2) has recently been identified in bats and horses, raising questions about its pathogenic potential. This study aimed to compare the disease severity caused by contemporary HeV-g1 and HeV-g2 isolates using the African green monkey (AGM) model. AGMs were experimentally infected via intranasal and intratracheal routes with either HeV-g1 or HeV-g2 and monitored for clinical signs, survival, viral replication, pathology, and immune responses. HeV-g1 infection resulted in uniformly severe and lethal disease, characterized by acute respiratory distress, systemic viral dissemination, and extensive tissue pathology. In contrast, HeV-g2 infection caused markedly milder disease, with most animals surviving and showing limited clinical signs, lower viral loads, and minimal pathological changes. Importantly, HeV-g2–infected animals mounted robust neutralizing antibody responses without detectable infectious virus in tissues. These findings demonstrate that contemporary HeV isolates can cause divergent clinical outcomes and indicate that HeV-g2 has reduced pathogenicity in primates compared with HeV-g1, providing critical insights for risk assessment and preparedness strategies.
(MN)