[Show abstract][Hide abstract] ABSTRACT: Hendra virus (HeV) is a highly pathogenic zoonotic paramyxovirus harbored by Australian flying foxes with sporadic spillovers directly to horses. Although the mode and critical control points of HeV spillover to horses from flying foxes, and the risk for transmission from infected horses to other horses and humans, are poorly understood, we successfully established systemic HeV disease in 3 horses exposed to Hendra virus/Australia/Horse/2008/Redlands by the oronasal route, a plausible route for natural infection. In 2 of the 3 animals, HeV RNA was detected continually in nasal swabs from as early as 2 days postexposure, indicating that systemic spread of the virus may be preceded by local viral replication in the nasal cavity or nasopharynx. Our data suggest that a critical factor for reducing HeV exposure risk to humans includes early consideration of HeV in the differential diagnosis and institution of appropriate infection control procedures.
[Show abstract][Hide abstract] ABSTRACT: Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50) within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.