Three decades of discovery: An overview of Hendra virus, the original Henipavirus

Hendra virus (HeV) emerged in Australia in 1994, causing a devastating outbreak among horses in Brisbane with spread to humans, resulting in one death. This nonsegmented, negative-stranded RNA virus belongs to the family Paramyxoviridae and represents the first zoonotic paramyxovirus isolated from bats. Flying foxes (genus Pteropus) serve as the natural reservoir, with all four mainland Australian species carrying antibodies with no apparent disease. HeV initiates infection by binding ephrin-B2 receptors on vascular endothelial cells, driving characteristic pathology involving vasculitis, thrombosis, and neurological complications. Horses are amplifying hosts, shedding virus abundantly in respiratory secretions and posing transmission risks to humans during invasive procedures. To date, seven confirmed human infections have been documented, with a 57% fatality rate, presenting as severe respiratory disease or progressive encephalitis. Two genetic variants are now recognized: the original HeV genotype 1 and the emerging HeV genotype 2, identified in limited equine cases. Recent surveillance of bat roosts revealed substantial viral diversity, with peak shedding occurring during winter-coinciding with equine spillover peaks. Prevention integrates multiple strategies: the licensed equine vaccine Equivac which provides One Health protection for both horses and human contacts; biosecurity measures including proper PPE; and habitat restoration to reduce nutritional stress in bat populations. Emerging therapeutics include monoclonal antibodies, with m102.4 showing cross-protective activity against both HeV and the closely related Nipah virus. No licensed human vaccines currently exist, though candidates are in development. Future prevention strategies increasingly recognize the importance of Indigenous-led conservation approaches alongside biomedical interventions. This review will focus on the history of HeV, virus replication and diversity, epidemiology, clinical manifestations, diagnosis, treatment, prevention, as well as ecological and interdisciplinary countermeasures.