Nipah and Hendra Viruses: Deadly Zoonotic Paramyxoviruses with the Potential to Cause the Next Pandemic

Abstract

Nipah and Hendra viruses are deadly zoonotic paramyxoviruses with a case fatality rate of upto 75%. The viruses belong to the genus henipavirus in the family Paramyxoviridae, a family of negative-sense single-stranded RNA viruses. The natural reservoirs of NiV and HeV are bats (flying foxes) in which the virus infection is asymptomatic. The intermediate hosts for NiV and HeV are swine and equine, respectively. In humans, NiV infections result in severe and often fatal respiratory and neurological manifestations. The Nipah virus was first identified in Malaysia and Singapore following an outbreak of encephalitis in pig farmers and subsequent outbreaks have been reported in Bangladesh and India almost every year. Due to its extreme pathogenicity, pandemic potential, and lack of established antiviral therapeutics and vaccines, research on henipaviruses is highly warranted so as to develop antivirals or vaccines that could aid in the prevention and control of future outbreaks.

Keywords: BSL-4; Cedar virus; Hendra virus; Nipah virus; vaccines.

Figure 1

Clinical presentation of Nipah virus (NiV) infections. A schematic depicting the clinical presentation of NiV infection is shown. Bats (flying foxes) are the natural reservoirs of NiV and are asymptomatic. In swine (Malaysia) and equine (Philippines),NiV infection is characterized by severe respiratory disease, cough, and neurological signs, while in humans fever, encephalitis (Malaysia), and acute respiratory disease (Bangladesh) have been reported.

Figure 2

Schematic representation of different Nipah virus (NiV) transmission routes. In Malaysia, pig farms lie in close proximity to fruit trees, which are resided by fruit bats and domestic pigs contract infection by coming into contact with materials contaminated by bats, particularly by consumption of bat-eaten fruits or by exposure to bat urine. NiV is subsequently transmitted from pigs to humans by direct contact. In India and Bangladesh, the major route of NiV transmission from bats to humans is by the consumption of raw date palm sap contaminated with bat saliva or urine followed by person-to person transmission occurring by close contact. In the Philippines, the source of human infection was traced to the consumption of horse meat or contact with infected horses, and then human-to-human transmission was reported from infected patients to healthy individuals.

Figure 3

Genome organization of henipa virions. A schematic depicting the gene order in henipaviruses is shown. Henipaviruses produce P, V, and W proteins as a result of mRNA editing (non-templated addition of Guanosine residues), while C protein is produced by leaky scanning (use of alternative start codons).

Figure 4

Replication cycle of henipaviruses: The viruses attach via G glycoproteins (shown in blue) to cellular receptors (ephrin B2/3). This triggers a conformational change in viral F proteins (shown in purple color), which allows the fusion of the viral envelope with the host cell plasma membrane, resulting in release of viral (−) RNA directly into the cell cytoplasm. This is followed by transcription to form mRNA followed by translation to allowthe formation of viral proteins. The F protein is produced in an inactive F0 precursor (pink), which is trafficked to the cell membrane from whichit is endocytosed and cleaved into active F1–F2 form by the cathepsin proteases present in the endosomes. The cleaved F proteins along with other viral proteins then assemble at the cell surface to allow budding and the release of henipa virions.