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Antiviral Research Oct 2013Hendra virus and Nipah virus are bat-borne paramyxoviruses that are the prototypic members of the genus Henipavirus. The henipaviruses emerged in the 1990s, spilling... (Review)
Review
Hendra virus and Nipah virus are bat-borne paramyxoviruses that are the prototypic members of the genus Henipavirus. The henipaviruses emerged in the 1990s, spilling over from their natural bat hosts and causing serious disease outbreaks in humans and livestock. Hendra virus emerged in Australia and since 1994 there have been 7 human infections with 4 case fatalities. Nipah virus first appeared in Malaysia and subsequent outbreaks have occurred in Bangladesh and India. In total, there have been an estimated 582 human cases of Nipah virus and of these, 54% were fatal. Their broad species tropism and ability to cause fatal respiratory and/or neurologic disease in humans and animals make them important transboundary biological threats. Recent experimental findings in animals have demonstrated that a human monoclonal antibody targeting the viral G glycoprotein is an effective post-exposure treatment against Hendra and Nipah virus infection. In addition, a subunit vaccine based on the G glycoprotein of Hendra virus affords protection against Hendra and Nipah virus challenge. The vaccine has been developed for use in horses in Australia and is the first vaccine against a Biosafety Level-4 (BSL-4) agent to be licensed and commercially deployed. Together, these advances offer viable approaches to address Hendra and Nipah virus infection of livestock and people.
Topics: Animals; Antibodies, Monoclonal; Cattle; Cattle Diseases; Hendra Virus; Henipavirus Infections; Humans; Nipah Virus; Viral Vaccines
PubMed: 23838047
DOI: 10.1016/j.antiviral.2013.06.012 -
MBio Jun 2022The Paramyxoviridae family comprises important pathogens that include measles (MeV), mumps, parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra...
The Paramyxoviridae family comprises important pathogens that include measles (MeV), mumps, parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra virus (HeV). Paramyxoviral entry into cells requires viral-cell membrane fusion, and formation of paramyxoviral pathognomonic syncytia requires cell-cell membrane fusion. Both events are coordinated by intricate interactions between the tetrameric attachment (G/H/HN) and trimeric fusion (F) glycoproteins. We report that receptor binding induces conformational changes in NiV G that expose its stalk domain, which triggers F through a cascade from prefusion to prehairpin intermediate (PHI) to postfusion conformations, executing membrane fusion. To decipher how the NiV G stalk may trigger F, we introduced cysteines along the G stalk to increase tetrameric strength and restrict stalk mobility. While most point mutants displayed near-wild-type levels of cell surface expression and receptor binding, most yielded increased NiV G oligomeric strength, and showed remarkably strong defects in syncytium formation. Furthermore, most of these mutants displayed stronger F/G interactions and significant defects in their ability to trigger F, indicating that NiV G stalk mobility is key to proper F triggering via moderate G/F interactions. Also remarkably, a mutant capable of triggering F and of fusion pore formation yielded little syncytium formation, implicating G or G/F interactions in a late step occurring post fusion pore formation, such as the extensive fusion pore expansion required for syncytium formation. This study uncovers novel mechanisms by which the G stalk and its oligomerization/mobility affect G/F interactions, the triggering of F, and a late fusion pore expansion step-exciting novel findings for paramyxoviral attachment glycoproteins. The important family includes measles, mumps, human parainfluenza, and the emerging deadly zoonotic Nipah virus (NiV) and Hendra virus (HeV). The deadly emerging NiV can cause neurologic and respiratory symptoms in humans with a >60% mortality rate. NiV has two surface proteins, the receptor binding protein (G) and fusion (F) glycoproteins. They mediate the required membrane fusion during viral entry into host cells and during syncytium formation, a hallmark of paramyxoviral and NiV infections. We previously discovered that the G stalk domain is important for triggering F (via largely unknown mechanisms) to induce membrane fusion. Here, we uncovered new roles and mechanisms by which the G stalk and its mobility modulate the triggering of F and also unexpectedly affect a very late step in membrane fusion, namely fusion pore expansion. Importantly, these novel findings may extend to other paramyxoviruses, offering new potential targets for therapeutic interventions.
Topics: Glycoproteins; Humans; Measles; Membrane Fusion; Mumps; Nipah Virus; Viral Envelope Proteins; Viral Fusion Proteins; Virus Attachment; Virus Internalization
PubMed: 35506666
DOI: 10.1128/mbio.03222-21 -
Releve Epidemiologique Hebdomadaire Feb 2004
Topics: Animals; Chiroptera; Disease Outbreaks; Hendra Virus; Henipavirus Infections; Humans; Malaysia; Nipah Virus; Zoonoses
PubMed: 15038065
DOI: No ID Found -
Proceedings of the National Academy of... Apr 2024Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and...
Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse, and hamster target cells using a different, yet unknown, receptor than Nipah virus (NiV) and Hendra virus (HeV) and that NiV- and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryoelectron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing their conformational landscape and distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs.
Topics: Humans; Animals; Mice; Cryoelectron Microscopy; Nipah Virus; Hendra Virus; Glycoproteins; Henipavirus Infections; Virus Internalization; Henipavirus
PubMed: 38593070
DOI: 10.1073/pnas.2314990121 -
Nature Communications Mar 2023Nipah virus (NiV) is a pathogenic paramyxovirus that causes fatal encephalitis in humans. Two envelope glycoproteins, the attachment protein (G/RBP) and fusion protein...
Nipah virus (NiV) is a pathogenic paramyxovirus that causes fatal encephalitis in humans. Two envelope glycoproteins, the attachment protein (G/RBP) and fusion protein (F), facilitate entry into host cells. Due to its vital role, NiV F presents an attractive target for developing vaccines and therapeutics. Several neutralization-sensitive epitopes on the NiV F apex have been described, however the antigenicity of most of the F protein's surface remains uncharacterized. Here, we immunize mice with prefusion-stabilized NiV F and isolate ten monoclonal antibodies that neutralize pseudotyped virus. Cryo-electron microscopy reveals eight neutralization-sensitive epitopes on NiV F, four of which have not previously been described. Novel sites span the lateral and basal faces of NiV F, expanding the known library of vulnerable epitopes. Seven of ten antibodies bind the Hendra virus (HeV) F protein. Multiple sequence alignment suggests that some of these newly identified neutralizing antibodies may also bind F proteins across the Henipavirus genus. This work identifies new epitopes as targets for therapeutics, provides a molecular basis for NiV neutralization, and lays a foundation for development of new cross-reactive antibodies targeting Henipavirus F proteins.
Topics: Humans; Animals; Mice; Nipah Virus; Epitopes; Cryoelectron Microscopy; Viral Envelope Proteins; Antibodies, Neutralizing; Antibodies, Monoclonal; Henipavirus Infections
PubMed: 36932063
DOI: 10.1038/s41467-023-36995-y -
Proceedings. Biological Sciences Jan 2015Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these... (Review)
Review
Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility.
Topics: Animals; Chiroptera; Humans; Models, Biological; Queensland; RNA Virus Infections; RNA Viruses; Zoonoses
PubMed: 25392474
DOI: 10.1098/rspb.2014.2124 -
Pathogens (Basel, Switzerland) Nov 2022Population growth and industrialization have led to a race for greater food and supply productivity. As a result, the occupation and population of forest areas, contact... (Review)
Review
Population growth and industrialization have led to a race for greater food and supply productivity. As a result, the occupation and population of forest areas, contact with wildlife and their respective parasites and vectors, the trafficking and consumption of wildlife, the pollution of water sources, and the accumulation of waste occur more frequently. Concurrently, the agricultural and livestock production for human consumption has accelerated, often in a disorderly way, leading to the deforestation of areas that are essential for the planet's climatic and ecological balance. The effects of human actions on other ecosystems such as the marine ecosystem cause equally serious damage, such as the pollution of this habitat, and the reduction of the supply of fish and other animals, causing the coastal population to move to the continent. The sum of these factors leads to an increase in the demands such as housing, basic sanitation, and medical assistance, making these populations underserved and vulnerable to the effects of global warming and to the emergence of emerging and re-emerging diseases. In this article, we discuss the anthropic actions such as climate changes, urbanization, deforestation, the trafficking and eating of wild animals, as well as unsustainable agricultural intensification which are drivers for emerging and re-emerging of zoonotic pathogens such as viral (Ebola virus, hantaviruses, Hendravirus, Nipah virus, rabies, and severe acute respiratory syndrome coronavirus disease-2), bacterial (leptospirosis, Lyme borreliosis, and tuberculosis), parasitic (leishmaniasis) and fungal pathogens, which pose a substantial threat to the global community. Finally, we shed light on the urgent demand for the implementation of the One Health concept as a collaborative global approach to raise awareness and educate people about the science behind and the battle against zoonotic pathogens to mitigate the threat for both humans and animals.
PubMed: 36422627
DOI: 10.3390/pathogens11111376 -
Viruses May 2023Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic species from the genus within the paramyxovirus family and are harbored by Flying Fox species....
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic species from the genus within the paramyxovirus family and are harbored by Flying Fox species. Henipaviruses cause severe respiratory disease, neural symptoms, and encephalitis in various animals and humans, with human mortality rates exceeding 70% in some NiV outbreaks. The henipavirus matrix protein (M), which drives viral assembly and budding of the virion, also performs non-structural functions as a type I interferon antagonist. Interestingly, M also undergoes nuclear trafficking that mediates critical monoubiquitination for downstream cell sorting, membrane association, and budding processes. Based on the NiV and HeV M X-ray crystal structures and cell-based assays, M possesses a putative monopartite nuclear localization signal (NLS) (residues KRKKIR; NLS1 HeV), positioned on an exposed flexible loop and typical of how many NLSs bind importin alpha (IMPα), and a putative bipartite NLS (RR-10X-KRK; NLS2 HeV), positioned within an α-helix that is far less typical. Here, we employed X-ray crystallography to determine the binding interface of these M NLSs and IMPα. The interaction of both NLS peptides with IMPα was established, with NLS1 binding the IMPα major binding site, and NLS2 binding as a non-classical NLS to the minor site. Co-immunoprecipitation (co-IP) and immunofluorescence assays (IFA) confirm the critical role of NLS2, and specifically K258. Additionally, localization studies demonstrated a supportive role for NLS1 in M nuclear localization. These studies provide additional insight into the critical mechanisms of M nucleocytoplasmic transport, the study of which can provide a greater understanding of viral pathogenesis and uncover a potential target for novel therapeutics for henipaviral diseases.
Topics: Animals; Humans; Nuclear Localization Signals; Active Transport, Cell Nucleus; Nipah Virus; alpha Karyopherins; Hendra Virus; Henipavirus Infections; Protein Binding
PubMed: 37376602
DOI: 10.3390/v15061302 -
Virulence Dec 2023A new virus, named Langya henipavirus (LayV), has recently been identified in Shandong and Henan provinces in China and has so far infected 35 individuals between April...
A new virus, named Langya henipavirus (LayV), has recently been identified in Shandong and Henan provinces in China and has so far infected 35 individuals between April 2018 and August 2021. It is closely related to other known henipaviruses (Nipah and Hendra viruses) that can cause up to 70% human case fatality. Even though LayV has not been shown to be fatal in humans and does not appear to be transmitted from human-to-human, it is an RNA virus with the capacity to evolve genetically in the infected hosts (e.g. shrews) and can infect humans (e.g. farmers who have been in close contacts with shrews). It is therefore important to be vigilant about this new viral outbreak.
Topics: Humans; Animals; Public Health; Shrews; Henipavirus Infections; Nipah Virus
PubMed: 36599832
DOI: 10.1080/21505594.2022.2154188 -
Reviews in Medical Virology Jan 2019Since emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population... (Review)
Review
Since emergence of the Nipah virus (NiV) in 1998 from Malaysia, the NiV virus has reappeared on different occasions causing severe infections in human population associated with high rate of mortality. NiV has been placed along with Hendra virus in genus Henipavirus of family Paramyxoviridae. Fruit bats (Genus Pteropus) are known to be natural host and reservoir of NiV. During the outbreaks from Malaysia and Singapore, the roles of pigs as intermediate host were confirmed. The infection transmitted from bats to pigs and subsequently from pigs to humans. Severe encephalitis was reported in NiV infection often associated with neurological disorders. First NiV outbreak in India occurred in Siliguri district of West Bengal in 2001, where direct transmission of the NiV virus from bats-to-human and human-to-human was reported in contrast to the role of pigs in the Malaysian NiV outbreak. Regular NiV outbreaks have been reported from Bangladesh since 2001 to 2015. The latest outbreak of NiV has been recorded in May, 2018 from Kerala, India which resulted in the death of 17 individuals. Due to lack of vaccines and effective antivirals, Nipah encephalitis poses a great threat to public health. Routine surveillance studies in the infected areas can be useful in detecting early signs of infection and help in containment of these outbreaks.
Topics: Animals; Asia; Chiroptera; Communicable Diseases, Emerging; Disease Outbreaks; Disease Transmission, Infectious; Epidemiological Monitoring; Henipavirus Infections; Humans; Nipah Virus; Survival Analysis; Swine; Swine Diseases; Zoonoses
PubMed: 30251294
DOI: 10.1002/rmv.2010