Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Nipah virus (NiV) is a zoonotic paramyxovirus that has recently emerged as a crucial public health issue. It can elicit severe encephalitis and respiratory diseases in animals and humans, leading to fatal outcomes, exhibiting a wide range of host species tropism, and directly transmitting from animals to humans or through an intermediate host. Human-to-human transmission associated with recurrent NiV outbreaks is a potential global health threat. Currently, the lack of effective therapeutics or licensed vaccines for NiV necessitates the primary utilization of supportive care. In this review, we summarize current knowledge of the various aspects of the NiV, including therapeutics, vaccines, and its biological characteristics, epidemiology, pathogenesis, and clinical features. The objective is to provide valuable information from scientific and clinical research and facilitate the formulation of strategies for preventing and controlling the NiV.
Animals ; Humans ; Disease Outbreaks/prevention & control* ; Henipavirus Infections/virology* ; Nipah Virus/pathogenicity* ; Viral Vaccines ; Zoonoses/virology*

Nipah virus disease (NVD) is a newly emerged zoonosis with a case fatality rate of 40%-75%. NVD is a severe threat to human health and the development of livestock farming. NVD has become one of the emerging infectious diseases with great concern globally during more than 20 years. Nipah virus (NiV) is a pathogen for NVD, the natural host of which is Fruit bats of the Pteropodidae family. The clinical spectrum of NiV infection is broad, including asymptomatic infection, acute respiratory infection, fatal encephalitis, and even death. Since NiV was first identified in Malaysia in 1999, it has been prevalent mainly in Southeast Asia and South Asia. NiV is primarily transmitted to humans through bat-pig-human, contaminated food. Currently, there are no specific therapeutic drugs and vaccines for NVD. Although there are no cases of NVD reported in China, which has close personnel and trade exchanges with major NVD-endemic countries, and NiV antibody has also been detected in relevant bats. There is a potential risk of importing NVD and domestic outbreaks in the future in this country. This paper provides a systematic review of the research progress in the prevention and control of NVD etiology, epidemiology, clinical manifestations and laboratory diagnosis to help relevant staff to understand NVD more comprehensively and systematically.
Animals ; Chiroptera ; Communicable Diseases, Emerging/prevention & control* ; Disease Outbreaks ; Henipavirus Infections/prevention & control* ; Nipah Virus ; Swine ; Zoonoses/prevention & control*

The two mammalian codon optimized genes, F and G genes of Nipah virus, were generated by assembly PCR, and inserted into mammalian expression vector pCAGGS under chicken beta-actin promoter to construct pCAGG-NiV-F and pCAGG-NiV-G. Syncytium formation was induced in BHK cells by plasmid pCAGG-NiV-F and pCAGG-NiV-G transfection, which indicate recombination proteins F and G were expressed in BHK cell and possessed good biologic activity. Six-week-old female BALB/c mice were intramuscularly primed with 100 microg pCAGG-NiV-F, pCAGG-NiV-G or pCAGG-NiV-F+ pCAGG-NiV-G respectively, and boosted with same dose after 4 weeks. The sera were collected at 3 weeks post second boost. The serum IgG against Nipah virus F and G proteins was detected by indirect ELISA using recombinant Baculovirus expressed Nipah F and G glycoproteins. The results showed that specific antibodies possessed good sensitivity and specificity. Furthermore, the G and F proteins' specific antibodies could neutralize the infectivity of VSVdeltaG* F/G (the NiV F and G envelope glycoproteins psudotyped recombinant vesicular stomatitis virus expressing green fluorescence protein). And, pCAGG-NiV-G also induced higher titer of neutralizing antibody response than pCAGG-NiV-F did. The result indicates that DAN immunization is an efficient vaccine strategy against Nipah virus.
Animals ; Antibodies, Viral ; blood ; Blotting, Western ; Enzyme-Linked Immunosorbent Assay ; Female ; Mice ; Mice, Inbred BALB C ; Nipah Virus ; immunology ; Vaccines, DNA ; immunology ; Viral Envelope Proteins ; genetics ; immunology ; Viral Vaccines ; immunology

In this study, Recombinant baculoviruses rBac-NF and rBac-NG were generated for expressing F and G proteins Nipah virus (NiV) . The expression of recommbinant G (rNG) and F (rNF) protein in rBac-NF and rBac-NG infected cells were confirmed by western-blot. Both rNG and rNF showed sensitive and specific antigenic reaction to rabbit serum anti-Nipah virus in indirect immunofluorescence detection and indirect ELISA. Immunization with rBac-NF and rBac-NG infected insect cells elicited G ad F protein specific antibody responses in mice. Furthermore, the G ad F specific antibodies could neutralize the infectivity of the VSVdeltaG* F/G, the NiV F and G envelope glycoproteins psudotyped recombinant Vesicular Stomatitis Virus expressing green fluorescence protein. The results demonstrated F and G protein expressed by the recombinant baculoviruses could be safe economic diagnostic antigens for the surveillance and monitoring of NiV and promising subunit vaccines for the prevention of NiV.
Animals ; Antigens, Viral ; immunology ; Baculoviridae ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Nipah Virus ; chemistry ; genetics ; Rabbits ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; Recombination, Genetic ; Viral Envelope Proteins ; biosynthesis ; genetics ; immunology

Animals ; Encephalitis, Viral ; epidemiology ; transmission ; virology ; Humans ; Incidence ; Malaysia ; epidemiology ; Nipah Virus ; isolation & purification