Henipaviruses: epidemiology, ecology, disease, and the development of vaccines and therapeutics

Abstract

SUMMARYHenipaviruses were first identified 30 years ago and have since been associated with over 30 outbreaks of disease in humans. Highly pathogenic henipaviruses include Hendra virus (HeV) and Nipah virus (NiV), classified as biosafety level 4 pathogens. In addition, NiV has been listed as a priority pathogen by the World Health Organization (WHO), the Coalition for Epidemic Preparedness Innovations (CEPI), and the UK Vaccines Research and Development Network (UKVN). Here, we re-examine epidemiological, ecological, clinical, and pathobiological studies of HeV and NiV to provide a comprehensive guide of the current knowledge and application to identify and evaluate countermeasures. We also discuss therapeutic and vaccine development efforts. Furthermore, with case identification, prevention, and treatment in mind, we highlight limitations in research and recognize gaps necessitating additional studies.

Keywords: Hendra virus; Nipah virus; animal model; antiviral; clinical disease; epidemiology; henipavirus; therapeutic; vaccine.

Fig 1

Henipavirus structure and phylogeny. (A) Henipavirus genomes are approximately 18,000 nucleotides in length and contain six genes: N, nucleocapsid protein; P, phosphoprotein; M, matrix protein; F, fusion glycoprotein; G, attachment glycoprotein; and RdRp, RNA-dependent RNA-polymerase. The P gene encodes three additional proteins, V, W, and C, translated via mRNA editing and an alternative start codon. Genes are separated by short intergenic regions, meaning each gene is preceded and followed by conserved transcriptional control signals involved in the initiation and termination of viral mRNA synthesis, respectively. At the genome termini, a 3′ leader sequence (3′Le) contains promoters for both transcription initiation as well as for the synthesis of the positive-sense replicative intermediate antigenome, and a 5′ trailer sequence (5′Tr) promotes the synthesis of new negative-sense genomes from the antigenome. Henipavirus virions are pleomorphic and consist of a viral lipid envelope containing multiple copies of the F and G, surrounding a single-stranded negative-sense RNA genome encapsidated by N and associated with P and RdRp. (B) Neighbor-joining phylogenies of full-length henipavirus genome nucleotide sequences showing relationships between all the genus Henipavirus species, as well as the previously recognized species Langya virus and Mòjiāng virus.

Fig 2

Reported henipavirus outbreaks in different countries from 1994 to 2022. Summary of geographic locations and year of report for henipavirus outbreaks involving human cases for Hendra virus (yellow—Australia), Nipah virus strain Malaysia (red—Malaysia, Singapore, and the Philippines), and Nipah virus strain Bangladesh (blue—India and Bangladesh).

Fig 3

Timeline of henipavirus virus vaccine development and clinical trials.