Paramyxoviruses: Henipaviruses

The henipaviruses are species of the genus Henipavirus within the Paramyxoviridae family. Henipavirus particles are enveloped and pleomorphic with an unsegmented, single-strand, negative-sense RNA genome and possess envelope glycoprotein projections that are essential for binding and cell entry. The natural reservoir of the three known henipaviruses, Hendra virus, Nipah virus and Cedar virus, are old world fruit bats of the genus Pteropus. Although the precise transmission pathway from bats to other animals is unknown, Pteropus bats intermittently shed henipavirus in urine and saliva. Hendra virus was discovered first in 1994 in eastern Australia and each of the recognized human cases of Hendra virus infection had heavy exposure to respiratory secretions from a Hendra virus-infected horse. Nipah virus was subsequently discovered as the cause of a large encephalitis outbreak affecting 283 people and leading to 109 (39 %) deaths in Malaysia in 1998. The observation that human cases of Nipah virus infection had more direct contact with pigs than controls and the isolation of Nipah virus from pigs' lungs, kidneys and respiratory secretions suggest that Nipah virus was transmitted from infected pigs to humans through contaminated saliva and possibly urine. Recurrent outbreaks of human Nipah virus infection with case fatality rates >70 % have been recognized in Bangladesh and India almost annually since 2001. Drinking raw date palm sap is the most common pathway of Nipah virus transmission from Pteropus bats to people identified in outbreak investigations. Nighttime infrared photography confirms that P. giganteus bats commonly visit date palm trees during collection and lick the sap stream. Person-to-person transmission of Nipah virus, apparently through respiratory secretions, has been repeatedly observed in Bangladesh and India. Henipaviruses manifest exceptionally broad species tropism, infecting vertebrate hosts spanning six mammalian orders. The henipaviruses bind to highly sequence-conserved ephrin-B2 and ephrin-B3 cell surface receptors using their attachment (G) envelope glycoproteins. Severe henipavirus infection in people presents as a severe respiratory disease, encephalitis, or both. If a patient recovers, henipavirus infection can later recrudesce as encephalitis. Preventing human henipavirus infection requires taking steps to limit fruit bat contact with human foods and domestic animals and minimizing exposure to excretion and secretions of sick animals that may have been exposed to fruit bats. Preliminary studies in animal models suggest that toll-like receptor 3 agonists and heptad fusion inhibiting peptides may prevent progression of henipavirus disease. A human monoclonal antibody (m102.4) has been remarkably effective as postexposure passive immunotherapy for both Nipah and Hendra virus in the African green monkey and ferret animal models. A subunit vaccine using a soluble oligomeric form of the G glycoprotein (sG) protects cats, ferrets, and African green monkeys in Nipah and Hendra challenge studies. Hendra virus-sG is now deployed as an equine/livestock vaccine. While human infections with henipavirus have a remarkably high case fatality rate, human infection is rare. This small number of human infections means that with limited budgets and competing priorities, prevention efforts have to be extremely low cost to be cost-effective.