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changing resource landscapes and spillover of henipaviruses.old world fruit bats (chiroptera: pteropodidae) provide critical pollination and seed dispersal services to forest ecosystems across africa, asia, and australia. in each of these regions, pteropodids have been identified as natural reservoir hosts for henipaviruses. the genus henipavirus includes hendra virus and nipah virus, which regularly spill over from bats to domestic animals and humans in australia and asia, and a suite of largely uncharacterized african henipaviruses. rapid change in fru ...201830138535
evolution of codon usage bias in henipaviruses is governed by natural selection and is host-specific.hendra virus (hev) and nipah virus (niv) are among a group of emerging bat-borne paramyxoviruses that have crossed their species-barrier several times by infecting several hosts with a high fatality rate in human beings. despite the fatal nature of their infection, a comprehensive study to explore their evolution and adaptation in different hosts is lacking. a study of codon usage patterns in henipaviruses may provide some fruitful insight into their evolutionary processes of synonymous codon us ...201830388838
viral regulation of host cell biology by hijacking of the nucleolar dna-damage response.recent studies indicate that nucleoli play critical roles in the dna-damage response (ddr) via interaction of ddr machinery including nbs1 with nucleolar treacle protein, a key mediator of ribosomal rna (rrna) transcription and processing. here, using proteomics, confocal and single molecule super-resolution imaging, and infection under biosafety level-4 containment, we show that this nucleolar ddr pathway is targeted by infectious pathogens. we find that the matrix proteins of hendra virus and ...201830076298
exploration of nucleoprotein α-more and xd interactions of nipah and hendra viruses.henipavirus, including hendra virus (hev) and nipah virus (niv), is a newly discovered human pathogen genus. the nucleoprotein of henipavirus contains an α-helical molecular recognition element (α-more) that folds upon binding to the x domain (xd) of the phosphoprotein (p). in order to explore the conformational dynamics of free α-mores and the underlying binding-folding mechanism with xd, atomic force field-based and hybrid structure-based md simulations were carried out. in our empirical force ...201829691656
using thermodynamic parameters to calibrate a mechanistic dose-response for infection of a host by a virus.assessing the risk of infection from emerging viruses or of existing viruses jumping the species barrier into novel hosts is limited by the lack of dose response data. the initial stages of the infection of a host by a virus involve a series of specific contact interactions between molecules in the host and on the virus surface. the strength of the interaction is quantified in the literature by the dissociation constant (kd) which is determined experimentally and is specific for a given virus mo ...201832289059
emerging infectious diseases: a review.this review highlights some of the recent concerning emerging infectious diseases, a number of them specifically that the world health organization has categorized as priorities for research.201832226656
a case series on the recent nipah epidemic in kerala.during may 2018 there occurred an outbreak in kerala, which started in soopikkada village, changarothu grama panchayath in perambra taluk, kozhikode district, of a febrile illness with altered sensorium and ards. the diagnosis was made from the second case that it is the dreaded nipah infection. following that 18 cases tested positive for nipah virus infection of which 2 survived. also there were four deaths with similar clinical picture but which occurred before the virus was identified. they w ...201831317711
nipah virus infection.nipah virus infection is an emerging zoonotic infection which presents with acute encephalitis and respiratory distress syndrome. it is associated with high mortality and classified as biosafety level 4 organisms in view of its features which make it a potential agent for bioterrorism. experience with broad spectrum antiviral agent ribavirin is promising in reducing the mortality and morbidity.201831313551
nipah virus (niv): a 'new' addition to the ever changing landscape of infections. 201831086681
towards global health security: response to the may 2018 nipah virus outbreak linked to pteropus bats in kerala, india. 201830483413
computational prediction of mirnas in nipah virus genome reveals possible interaction with human genes involved in encephalitis.current re-emergence of nipah virus (niv) in india caused 11 deaths so far and many patients were kept in quarantine. a thorough study of previous outbreaks occurred in malaysia, bangladesh and india represents cases with high rate of fatality due to acute encephalitis. our work involves genome analysis of niv for prediction of mirnas and their targeted genes in human in order to understand encephalitis origin. ab-intio program-vmir was used for initial screening of genome, obtained nine pre-mir ...201830426028
epitope-based immunoinformatics approach on rna-dependent rna polymerase (rdrp) protein complex of nipah virus (niv).persistent outbreaks of nipah virus (niv) with severe case fatality throw a major challenge on researchers to develop a drug or vaccine to combat the disease. with little knowledge of its molecular mechanisms, we utilized the proteome data of niv to evaluate the potency of three major proteins (phosphoprotein, polymerase, and nucleocapsid protein) in the rna-dependent rna polymerase complex to count as a possible candidate for epitope-based vaccine design. profound computational analysis was use ...201830417438
the killer virus called nipah: a review.nipah virus (niv) is a deadly virus with a high mortality rate that has affected many developing countries in the past. according to the centers for disease control and prevention (cdc), many economically deprived countries such as madagascar, cambodia, and thailand are also at high risk for future outbreaks. the first case of niv was reported in 1998 and almost two decades later, little scientific progress has been made in finding a proper treatment and prevention vaccine. as many developing co ...201830416895
mapping disease transmission risk of nipah virus in south and southeast asia.since 1998, nipah virus (niv) (genus: henipavirus; family: paramyxoviridae), an often-fatal and highly virulent zoonotic pathogen, has caused sporadic outbreak events. fruit bats from the genus pteropus are the wildlife reservoirs and have a broad distribution throughout south and southeast asia, and east africa. understanding the disease biogeography of niv is critical to comprehending the potential geographic distribution of this dangerous zoonosis. this study implemented the r packages enmeva ...201830274453
what is new in infectious diseases: nipah virus, mers-cov and the blueprint list of the world health organization.not available.201830246760
nipah virus: a new threat to south asia. 201830089418
a stochastic assembly model for nipah virus revealed by super-resolution microscopy.understanding virus assembly mechanisms is important for developing therapeutic interventions. nipah virus (niv) is of interest because of its high mortality rate and efficient human-human transmissions. the current model for most enveloped viruses suggests that matrix proteins (m) recruit attachment glycoproteins (g) and fusion glycoproteins (f) to the assembly site at the plasma membrane. here we report an assembly model that differs in many aspects from the current one. examining niv proteins ...201830076303
sendai virus v protein inhibits the secretion of interleukin-1β by preventing nlrp3 inflammasome assembly.inflammasomes play a key role in host innate immune responses to viral infection by caspase-1 (casp-1) activation to facilitate interleukin-1β (il-1β) secretion, which contributes to the host antiviral defense. the nlrp3 inflammasome consists of the cytoplasmic sensor molecule nlrp3, adaptor protein asc, and effector protein pro-caspase-1 (pro-casp-1). nlrp3 and asc promote pro-casp-1 cleavage, leading to il-1β maturation and secretion. however, as a countermeasure, viral pathogens have evolved ...201830021903
nipah virus in kerala: a deadly zoonosis. 201829935330
nipah virus control needs more than r&d. 201829900857
enhancing preparation for large nipah outbreaks beyond bangladesh: preventing a tragedy like ebola in west africa.the nipah virus has been transmitted from person-to-person via close contact in non-urban parts of india (including kerala may 2018), bangladesh, and the philippines. it can cause encephalitis and pneumonia, and has a high case fatality rate. nipah is a one health zoonotic infectious disease linked to fruit bats, and sometimes pigs or horses. we advocate anticipating and preparing for urban and larger rural outbreaks of nipah. immediate enhanced preparations would include standardized guidance o ...201829879523
sixty seconds on . . . nipah virus. 201829871862
nipah virus outbreak in india. 201831876482
position paper on road map for rna virus research in india.the indian subcontinent with its population density, climatic conditions, means of subsistence, socioeconomic factors as well as travel and tourism presents a fertile ground for thriving of rna viruses. despite being pathogens of huge significance, there is very little focus on research into the biology and pathogenesis of rna viruses in india. studies on epidemiology and disease burden, risk factors, the immune response to rna viruses, circulating virus strains and virus evolution, animal model ...201830131779
tackling nipah virus: £2.36 million grant awarded to pirbright to create vaccine. 201728883102
international health threats and global early warning and response mechanisms.the global community continues to incur the high costs of crisis mitigation and emergency response to outbreaks of emerging infectious diseases, such as those caused by the h5n1 highly pathogenic avian influenza virus, ebola virus, nipah virus, zika virus or the middle east respiratory syndrome coronavirus. these viruses are particularly dangerous in regions associated with poor development indicators and high vulnerability. the drivers of these disease crises include failures in the way that an ...201730152454
a large-scale behavior change intervention to prevent nipah transmission in bangladesh: components and costs.nipah virus infection (niv) is a bat-borne zoonosis transmitted to humans through consumption of niv-contaminated raw date palm sap in bangladesh. the objective of this analysis was to measure the cost of an niv prevention intervention and estimate the cost of scaling it up to districts where spillover had been identified.201728651646
convergence of humans, bats, trees, and culture in nipah virus transmission, bangladesh.preventing emergence of new zoonotic viruses depends on understanding determinants for human risk. nipah virus (niv) is a lethal zoonotic pathogen that has spilled over from bats into human populations, with limited person-to-person transmission. we examined ecologic and human behavioral drivers of geographic variation for risk of niv infection in bangladesh. we visited 60 villages during 2011-2013 where cases of infection with niv were identified and 147 control villages. we compared case villa ...201728820130
antiviral lipopeptide-cell membrane interaction is influenced by peg linker length.a set of lipopeptides was recently reported for their broad-spectrum antiviral activity against viruses belonging to the paramyxoviridae family, including human parainfluenza virus type 3 and nipah virus. among them, the peptide with a 24-unit peg linker connecting it to a cholesterol moiety (vg-peg24-chol) was found to be the best membrane fusion inhibitory peptide. here, we evaluated the interaction of the same set of peptides with biomembrane model systems and isolated human peripheral blood ...201728714870
mutations in the transmembrane domain and cytoplasmic tail of hendra virus fusion protein disrupt virus-like-particle assembly.hendra virus (hev) is a zoonotic paramyxovirus that causes deadly illness in horses and humans. an intriguing feature of hev is the utilization of endosomal protease for activation of the viral fusion protein (f). here we investigated how endosomal f trafficking affects hev assembly. we found that the hev matrix (m) and f proteins each induced particle release when they were expressed alone but that their coexpression led to coordinated assembly of virus-like particles (vlps) that were morpholog ...201728468881
4'-azidocytidine (r1479) inhibits henipaviruses and other paramyxoviruses with high potency.the henipaviruses nipah virus and hendra virus are highly pathogenic zoonotic paramyxoviruses which have caused fatal outbreaks of encephalitis and respiratory disease in humans. despite the availability of a licensed equine hendra virus vaccine and a neutralizing monoclonal antibody shown to be efficacious against henipavirus infections in non-human primates, there remains no approved therapeutics or vaccines for human use. to explore the possibility of developing small-molecule nucleoside inhi ...201728629988
hendra and nipah virus infection in cultured human olfactory epithelial cells.henipaviruses are emerging zoonotic viruses and causative agents of encephalitis in humans. however, the mechanisms of entry into the central nervous system (cns) in humans are not known. here, we evaluated the possible role of olfactory epithelium in virus entry into the cns. we characterized hendra virus (hev) and nipah virus (niv) infection of primary human olfactory epithelial cultures. we show that henipaviruses can infect mature olfactory sensory neurons. henipaviruses replicated efficient ...201728680971
in silico identification and characterization of common epitope-based peptide vaccine for nipah and hendra viruses.to explore a common b- and t-cell epitope-based vaccine that can elicit an immune response against encephalitis causing genus henipaviruses, hendra virus (hev) and nipah virus (niv).201728756915
nipah and hendra virus nucleoproteins inhibit nuclear accumulation of stat1 and stat2 by interfering with their complex formation.henipaviruses, such as nipah (niv) and hendra (hev) viruses, are highly pathogenic zoonotic agents within the paramyxoviridae family. the phosphoprotein (p) gene products of the paramyxoviruses have been well characterized in their interferon (ifn) antagonist activity and their contribution to viral pathogenicity. in this study, we demonstrated that the nucleoprotein (n) of henipaviruses also prevents the host ifn signaling pathway. reporter assays demonstrated that niv and hev n proteins (niv-n ...201728835499
physiological stress and hendra virus in flying-foxes (pteropus spp.), australia.pteropid bats (flying-foxes) are the natural reservoir of hendra virus, an emergent paramyxovirus responsible for fatal infection in horses and humans in australia. pteropus alecto (the black flying-fox) and the paraphyletic p. conspicillatus (the spectacled flying-fox) appear to be the primary reservoir hosts. previous studies have suggested that physiological and ecological factors may underpin infection dynamics in flying-foxes, and subsequent spillover to horses and in turn humans. we sought ...201728767708
novel alphacoronaviruses and paramyxoviruses cocirculate with type 1 and severe acute respiratory system (sars)-related betacoronaviruses in synanthropic bats of luxembourg.several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. in this study from luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species rhinolophus ferrumequinum and myotis emarginatus were evaluated. feces collection (n = 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. in addition, feces (n = 254) were collected cross-sect ...201728710271
preliminary study of malaysian fruit bats species diversity in lenggong livestock breeding center, perak: potential risk of spill over infection.farms that are neighboring wildlife sanctuaries are at risk of spillover infection from wildlife, and the objective of this research is to examine the species diversity of malaysian fruit bats in livestock farm in determining the possible risk of spill over infection to livestock.201729263588
a controlled trial to reduce the risk of human nipah virus exposure in bangladesh.human nipah virus (niv) infection, often fatal in bangladesh, is primarily transmitted by drinking raw date palm sap contaminated by pteropus bats. we assessed the impact of a behavior change communication intervention on reducing consumption of potentially niv-contaminated raw sap. during the 2012-2014 sap harvesting seasons, we implemented interventions in two areas and compared results with a control area. in one area, we disseminated a "do not drink raw sap" message and, in the other area, e ...201728905152
a vlp-based vaccine provides complete protection against nipah virus challenge following multiple-dose or single-dose vaccination schedules in a hamster model.nipah virus is a highly lethal zoonotic paramyxovirus that was first recognized in malaysia during an outbreak in 1998. during this outbreak, nipah virus infection caused a severe febrile neurological disease in humans who worked in close contact with infected pigs. the case fatality rate in humans was approximately 40%. since 2001, niv has re-emerged in bangladesh and india where fruit bats (pteropus spp.) have been identified as the principal reservoir of the virus. transmission to humans is c ...201729263876
nipah virus outbreaks in bangladesh: a deadly infectious disease.during 2001-2011, multidisciplinary teams from the institute of epidemiology, disease control and research (iedcr) and international centre for diarrhoeal disease research, bangladesh(icddr,b) identified sporadic cases and 11 outbreaks of nipah encephalitis. three outbreaks were detected through sentinel surveillance; others were identified through event-based surveillance. a total of 196 cases of nipah encephalitis, in outbreaks, clusters and as isolated cases were detected from 20 districts of ...201728612796
exploring the human-nipah virus protein-protein interactome.nipah virus is an emerging, highly pathogenic, zoonotic virus of theparamyxoviridaefamily. human transmission occurs by close contact with infected animals, the consumption of contaminated food, or, occasionally, via other infected individuals. currently, we lack therapeutic or prophylactic treatments for nipah virus. to develop these agents we must now improve our understanding of the host-virus interactions that underpin a productive infection. this aim led us to perform the present work, in w ...201728904190
monomeric ephrinb2 binding induces allosteric changes in nipah virus g that precede its full activation.nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. two glycoproteins coordinate the infection of host cells, an attachment protein (g), which binds to cell surface receptors, and a fusion (f) protein, which carries out the process of virus-cell membrane fusion. the g protein binds to ephrin b2/3 receptors, inducing g conformational changes that trigger f protein refolding. using an optical approach based on second harmonic generation, w ...201728974687
variability of interferon-λ induction and antiviral activity in nipah virus infected differentiated human bronchial epithelial cells of two human donors.highly pathogenic nipah virus (niv) generally causes severe encephalitis in humans. respiratory symptoms are infrequently observed, likely reflecting variations in infection kinetics in human airways. supporting this idea, we recently identified individual differences in niv replication kinetics in cultured airway epithelia from different human donors. as type iii interferons (ifn-λ) represent major players in the defence mechanism against viral infection of the respiratory mucosa, we studied if ...201728984239
transmission of henipaviruses.the genus henipavirus has expanded rapidly in geographic range, number of species, and host range. hendra and nipah virus are two henipaviruses known to cause severe disease in humans with a high case-fatality rate. pteropid spp. bats are the natural reservoir of hendra and nipah virus. from these bats, virus can be transmitted to an amplifying host, horses and pigs, and from these hosts to humans, or the virus can be transmitted directly to humans. although the main route of shedding varies bet ...201729035743
kanyawara virus: a novel rhabdovirus infecting newly discovered nycteribiid bat flies infesting previously unknown pteropodid bats in uganda.bats are natural reservoir hosts of highly virulent pathogens such as marburg virus, nipah virus, and sars coronavirus. however, little is known about the role of bat ectoparasites in transmitting and maintaining such viruses. the intricate relationship between bats and their ectoparasites suggests that ectoparasites might serve as viral vectors, but evidence to date is scant. bat flies, in particular, are highly specialized obligate hematophagous ectoparasites that incidentally bite humans. usi ...201728706276
offering patients more: how the west africa ebola outbreak can shape innovation in therapeutic research for emerging and epidemic infections.although, after an epidemic of over 28 000 cases, there are still no licensed treatments for ebola virus disease (evd), significant progress was made during the west africa outbreak. the pace of pre-clinical development was exceptional and a number of therapeutic clinical trials were conducted in the face of considerable challenges. given the on-going risk of emerging infectious disease outbreaks in an era of unprecedented population density, international travel and human impact on the environm ...201728396467
evaluation of a taqman array card for detection of central nervous system infections.infections of the central nervous system (cns) are often acute, with significant morbidity and mortality. routine diagnosis of such infections is limited in developing countries and requires modern equipment in advanced laboratories that may be unavailable to a number of patients in sub-saharan africa. we developed a taqman array card (tac) that detects multiple pathogens simultaneously from cerebrospinal fluid. the 21-pathogen cns multiple-pathogen tac (cns-tac) assay includes two parasites (ba ...201728404679
cryptic etiopathological conditions of equine nervous system with special emphasis on viral diseases.the importance of horse (equus caballus) to equine practitioners and researchers cannot be ignored. an unevenly distributed population of equids harbors numerous diseases, which can affect horses of any age and breed. among these, the affections of nervous system are potent reason for death and euthanasia in equids. many episodes associated with the emergence of equine encephalitic conditions have also pose a threat to human population as well, which signifies their pathogenic zoonotic potential ...201729391683
contribution of human lung parenchyma and leukocyte influx to oxidative stress and immune system-mediated pathology following nipah virus infection.nipah virus (niv) is a zoonotic emerging paramyxovirus that can cause fatal respiratory illness or encephalitis in humans. despite many efforts, the molecular mechanisms of niv-induced acute lung injury (ali) remain unclear. we previously showed that niv replicates to high titers in human lung grafts in nod-scid/γ mice, resulting in a robust inflammatory response. interestingly, these mice can undergo human immune system reconstitution by the bone marrow, liver, and thymus (blt) reconstitution m ...201728539439
gene end-like sequences within the 3' non-coding region of the nipah virus genome attenuate viral gene transcription.the regulation of transcription during nipah virus (niv) replication is poorly understood. using a bicistronic minigenome system, we investigated the involvement of non-coding regions (ncrs) in the transcriptional re-initiation efficiency of niv rna polymerase. reporter assays revealed that attenuation of niv gene expression was not constant at each gene junction, and that the attenuating property was controlled by the 3' ncr. however, this regulation was independent of the gene-end, gene-start ...201728494343
loss in lung volume and changes in the immune response demonstrate disease progression in african green monkeys infected by small-particle aerosol and intratracheal exposure to nipah virus.nipah virus (niv) is a paramyxovirus (genus henipavirus) that emerged in the late 1990s in malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in bangladesh and india. niv infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of niv contaminated foods. in the work presented here, the development of disease was investigated in the a ...201728388650
broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides.human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like nipah virus. infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. paramyxovirus viral fusion proteins (f) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure th ...201728344321
cytoplasmic motifs in the nipah virus fusion protein modulate virus particle assembly and egress.nipah virus (niv), a paramyxovirus in the genus henipavirus, has a mortality rate in humans of approximately 75%. while several studies have begun our understanding of niv particle formation, the mechanism of this process remains to be fully elucidated. for many paramyxoviruses, m proteins drive viral assembly and egress; however, some paramyxoviral glycoproteins have been reported as important or essential in budding. for niv the matrix protein (m), the fusion glycoprotein (f), and to a much le ...201728250132
antibodies against henipa-like viruses in brazilian bats.bats are reservoir hosts for many paramyxoviruses, some of which cause human and zoonotic diseases of public health importance. we developed a nipah virus nucleoprotein enzyme-linked immunosorbent assay to detect cross-reactive antibodies in serum samples from several bat species in brazil. our results warrant further investigation of henipa-like virus reservoirs in the western hemisphere.201728103156
nipah virus: transmission of a zoonotic paramyxovirus.nipah virus is a recently-recognised, zoonotic paramyxovirus that causes severe disease and high fatality rates in people. outbreaks have occurred in malaysia, singapore, india and bangladesh, and a putative nipah virus was also recently associated with human disease in the philippines. worryingly, human-to-human transmission is common in bangladesh, where outbreaks occur with near-annual frequency. onward human transmission of nipah virus in bangladesh is associated with close contact with clin ...201728088124
understanding the interaction between henipaviruses and their natural host, fruit bats: paving the way toward control of highly lethal infection in humans.hendra virus and nipah virus (niv) are highly pathogenic zoonotic paramyxoviruses, from henipavirus genus, that have emerged in late 1990s in australia and south-east asia, respectively. since their initial identification, numerous outbreaks have been reported, affecting both domestic animals and humans, and multiple rounds of person-to-person niv transmission were observed. widely distributed fruit bats from pteropodidae family were found to be henipavirus natural reservoir. numerous studies ha ...201728060559
nuclear localization and secretion competence is conserved amongst henipavirus matrix proteins.viruses of the genus henipavirus of the family paramyxoviridae are zoonotic pathogens, which have emerged in south east asia, australia and africa. nipah virus (niv) and hendra virus (hev) are highly virulent pathogens transmitted from bats to animals and humans, whilst the henipavirus cedar virus (cedv) seems to be non-pathogenic in infection studies. the full replication cycle of the paramyxoviridae occurs in the host cell's cytoplasm where viral assembly is orchestrated by the matrix (m) prot ...201728056216
identification of the cell binding domain in nipah virus g glycoprotein using a phage display system.nipah virus (niv) is a highly pathogenic zoonotic paramyxovirus with unusual broad host tropism and is designated as a category c pathogen by the u.s. national institute of allergy and infectious diseases. niv infection is initiated after binding of the viral g glycoprotein to the host cell receptor. the aim of this study was to map the niv g glycoprotein cell binding domain using a phage display system. the niv g extracellular domain was truncated and displayed as attachment proteins on m13 pha ...201728082163
serum from nipah virus patients recognises recombinant viral proteins produced in escherichia coli.the genes for nipah virus (niv) proteins were amplified from viral rna, cloned into the plasmid ptriex-3 hygro, expressed, and purified using immobilized metal affinity chromatography. the recombinant n, f, and g niv proteins (rniv-n, rniv-f, and rniv-g), were successfully expressed in escherichia coli and purified with a yield of 4, 16, and 4 mg/l, respectively. all 3 recombinant viral proteins reacted with all 19 samples of niv-positive human sera. the rniv-n and rniv-g proteins were the most ...201727169942
a review of the current status of relevant zoonotic pathogens in wild swine (sus scrofa) populations: changes modulating the risk of transmission to humans.many wild swine populations in different parts of the world have experienced an unprecedented demographic explosion that may result in increased exposure of humans to wild swine zoonotic pathogens. interactions between humans and wild swine leading to pathogen transmission could come from different ways, being hunters and game professionals the most exposed to acquiring infections from wild swine. however, increasing human settlements in semi-natural areas, outdoor activities, socio-economic cha ...201725953392
chikungunya, influenza, nipah, and semliki forest chimeric viruses with vesicular stomatitis virus: actions in the brain.recombinant vesicular stomatitis virus (vsv)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. however, the critical safety concern is the neurotropic nature conveyed by the vsv glycoprotein. vsvs that include the vsv glycoprotein (g) gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. here, we test 4 chimeric viruses in the brain, including those in which glycoprotein gen ...201728077641
production of the virus-like particles of nipah virus matrix protein in pichia pastoris as diagnostic reagents.the matrix (m) protein of nipah virus (niv) is a peripheral protein that plays a vital role in the envelopment of nucleocapsid protein and acts as a bridge between the viral surface and the nucleocapsid proteins. the m protein is also proven to play an important role in production of virus-like particles (vlps) and is essential for assembly and budding of niv particles. the recombinant m protein produced in escherichia coli assembled into vlps in the absence of the viral surface proteins. howeve ...201627088434
development and evaluation of recombinant nucleocapsid protein based diagnostic elisa for detection of nipah virus infection in pigs.the recombinant viral protein-based indirect enzyme-linked immunosorbent assay (elisa) is a cost-effective, safe, specific, and rapid tool to diagnose the viral infection. nipah virus nucleocapsid (niv-n) protein was expressed in escherichia coli and purified by histidine tag-based affinity chromatography. the n protein was selected based on its immuno dominance and conservation among different niv strains. an indirect immunoglobulin g (igg) enzyme-linked immunosorbent assay (elisa) for swine se ...201626327601
protection against henipaviruses in swine requires both, cell-mediated and humoral immune response.hendra virus (hev) and nipah virus (niv) are members of the genus henipavirus, within the family paramyxoviridae. nipah virus has caused outbreaks of human disease in bangladesh, malaysia, singapore, india and philippines, in addition to a large outbreak in swine in malaysia in 1998/1999. recently, niv was suspected to be a causative agent of an outbreak in horses in 2014 in the philippines, while hev has caused multiple human and equine outbreaks in australia since 1994. a swine vaccine able to ...201627544586
detection of severe acute respiratory syndrome-like, middle east respiratory syndrome-like bat coronaviruses and group h rotavirus in faeces of korean bats.bat species around the world have recently been recognized as major reservoirs of several zoonotic viruses, such as severe acute respiratory syndrome coronavirus (sars-cov), middle east respiratory syndrome coronavirus (mers-cov), nipah virus and hendra virus. in this study, consensus primer-based reverse transcriptase polymerase chain reactions (rt-pcrs) and high-throughput sequencing were performed to investigate viruses in bat faecal samples collected at 11 natural bat habitat sites from july ...201627213718
hendra virus and nipah virus animal vaccines.hendra virus (hev) and nipah virus (niv) are zoonotic viruses that emerged in the mid to late 1990s causing disease outbreaks in livestock and people. hev appeared in queensland, australia in 1994 causing a severe respiratory disease in horses along with a human case fatality. niv emerged a few years later in malaysia and singapore in 1998-1999 causing a large outbreak of encephalitis with high mortality in people and also respiratory disease in pigs which served as amplifying hosts. the key pat ...201627154393
two highly similar laeddtnaqkt and ltdkigtei epitopes in g glycoprotein may be useful for effective epitope based vaccine design against pathogenic henipavirus.nipah virus and hendra virus, two members of the genus henipavirus, are newly emerging zoonotic pathogens which cause acute respiratory illness and severe encephalitis in human. lack of the effective antiviral therapy endorses the urgency for the development of vaccine against these deadly viruses. in this study, we employed various computational approaches to identify epitopes which has the potential for vaccine development. by analyzing the immune parameters of the conserved sequences of g gly ...201626970211
c-terminal dxd-containing sequences within paramyxovirus nucleocapsid proteins determine matrix protein compatibility and can direct foreign proteins into budding particles.paramyxovirus particles are formed by a budding process coordinated by viral matrix (m) proteins. m proteins coalesce at sites underlying infected cell membranes and induce other viral components, including viral glycoproteins and viral ribonucleoprotein complexes (vrnps), to assemble at these locations from which particles bud. m proteins interact with the nucleocapsid (np or n) components of vrnps, and these interactions enable production of infectious, genome-containing virions. for the param ...201626792745
structure and stabilization of the hendra virus f glycoprotein in its prefusion form.hendra virus (hev) is one of the two prototypical members of the henipavirus genus of paramyxoviruses, which are designated biosafety level 4 (bsl-4) organisms due to the high mortality rate of nipah virus (niv) and hev in humans. paramyxovirus cell entry is mediated by the fusion protein, f, in response to binding of a host receptor by the attachment protein. during posttranslational processing, the fusion peptide of f is released and, upon receptor-induced triggering, inserts into the host cel ...201626712026
the immune evasion function of j and beilong virus v proteins is distinct from that of other paramyxoviruses, consistent with their inclusion in the proposed genus jeilongvirus.ifn-antagonist function is a major determinant of pathogenicity and cross-species infection by viruses, but remains poorly defined for many potentially zoonotic viruses resident in animal species. the paramyxovirus family contains several zoonotic viruses, including highly pathogenic viruses such as nipah virus and hendra virus, and an increasing number of largely uncharacterized animal viruses. here, we report the characterization of ifn antagonism by the rodent viruses j virus (jpv) and beilon ...201626703878
expression, characterisation and antigenicity of a truncated hendra virus attachment protein expressed in the protozoan host leishmania tarentolae.hendra virus (hev) is an emerging zoonotic paramyxovirus within the genus henipavirus that has caused severe morbidity and mortality in humans and horses in australia since 1994. hev infection of host cells is mediated by the membrane bound attachment (g) and fusion (f) glycoproteins, that are essential for receptor binding and fusion of viral and cellular membranes. the eukaryotic unicellular parasite leishmania tarentolae has recently been established as a powerful tool to express recombinant ...201626585033
isolation of tioman virus from pteropus giganteus bat in north-east region of india.bat-borne viral diseases are a major public health concern among newly emerging infectious diseases which includes severe acute respiratory syndrome, nipah, marburg and ebola virus disease. during the survey for nipah virus among bats at north-east region of india; tioman virus (tiov), a new member of the paramyxoviridae family was isolated from tissues of pteropus giganteus bats for the first time in india. this isolate was identified and confirmed by rt-pcr, sequence analysis and electron micr ...201627619056
ensemble structure of the highly flexible complex formed between vesicular stomatitis virus unassembled nucleoprotein and its phosphoprotein chaperone.nucleocapsid assembly is an essential process in the replication of the non-segmented, negative-sense rna viruses (nnvs). unassembled nucleoprotein (n(0)) is maintained in an rna-free and monomeric form by its viral chaperone, the phosphoprotein (p), forming the n(0)-p complex. our earlier work solved the structure of vesicular stomatitis virus complex formed between an n-terminally truncated n (nδ21) and a peptide of p (p60) encompassing the n(0)-binding site, but how the full-length p interact ...201627107640
single-vector, single-injection recombinant vesicular stomatitis virus vaccines against high-containment viruses.there are many avenues for making an effective vaccine against viruses. depending on the virus these can include one of the following: inactivation of whole virions; attenuation of viruses; recombinant viral proteins; non-replication-competent virus particles; or surrogate virus vector systems such as vesicular stomatitis virus (vsv). vsv is a prototypic enveloped animal virus that has been used for over four decades to study virus replication, entry, and assembly due to its ability to replicate ...201627076138
pseudotyping viral vectors with emerging virus envelope proteins.previously unidentified viruses, such as middle east respiratory syndrome coronavirus, continue to emerge and threaten populations, while powerful new techniques have identified many new human and animal viruses. similarly, existing viruses, from ebola virus to chikungunya virus, are reemerging and spreading to new geographical regions. these viruses often pose a challenge for researchers to study due to their highly pathogenic nature. lentiviral and rhabdoviral pseudotypes are excellent tools f ...201626785737
taking forward a 'one health' approach for turning the tide against the middle east respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential.the appearance of novel pathogens of humans with epidemic potential and high mortality rates have threatened global health security for centuries. over the past few decades new zoonotic infectious diseases of humans caused by pathogens arising from animal reservoirs have included west nile virus, yellow fever virus, ebola virus, nipah virus, lassa fever virus, hanta virus, dengue fever virus, rift valley fever virus, crimean-congo haemorrhagic fever virus, severe acute respiratory syndrome coron ...201627321961
receptor-targeted nipah virus glycoproteins improve cell-type selective gene delivery and reveal a preference for membrane-proximal cell attachment.receptor-targeted lentiviral vectors (lvs) can be an effective tool for selective transfer of genes into distinct cell types of choice. moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. here we show that lvs pseudotyped with receptor-targeted nipah virus (niv) glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell memb ...201627281338
dual microrna screens reveal that the immune-responsive mir-181 promotes henipavirus entry and cell-cell fusion.hendra and nipah viruses (family paramyxoviridae, genus henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded micrornas (mirnas) impacting henipavirus infection in human cells. ...201627783670
transcriptional analysis of antiviral small molecule therapeutics as agonists of the rlr pathway.the recognition of pathogen associated molecular patterns (pamps) by pattern recognition receptors (prr) during viral infection initiates the induction of antiviral signaling pathways, including activation of the interferon regulator factor 3 (irf3). we identified small molecule compounds that activate irf3 through mavs, thereby inhibiting infection by viruses of the families flaviviridae (west nile virus, dengue virus and hepatitis c virus), filoviridae (ebola virus), orthomyxoviridae (influenz ...201626981429
a generic quantitative risk assessment framework for the entry of bat-borne zoonotic viruses into the european union.bat-borne viruses have been linked to a number of zoonotic diseases; in 2014 there have been human cases of nipah virus (niv) in bangladesh and ebola virus in west and central africa. here we describe a model designed to provide initial quantitative predictions of the risk of entry of such viruses to european union (eu) member states (mss) through four routes: human travel, legal trade (e.g. fruit and animal products), live animal movements and illegal importation of bushmeat. the model utilises ...201627788234
a reverse genetics approach for the design of methyltransferase-defective live attenuated avian metapneumovirus vaccines.avian metapneumovirus (ampv), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. ampv belongs to the family paramyxoviridae which includes many important human pathogens such as human respiratory syncytial virus (rsv), human metapneumovirus (hmpv), and human parainfluenza virus type 3 (piv3). the family also includes highly lethal emerging pathogens such as nipah virus and hen ...201627076293
morbillivirus and henipavirus attachment protein cytoplasmic domains differently affect protein expression, fusion support and particle assembly.the amino-terminal cytoplasmic domains of paramyxovirus attachment glycoproteins include trafficking signals that influence protein processing and cell surface expression. to characterize the role of the cytoplasmic domain in protein expression, fusion support and particle assembly in more detail, we constructed chimeric nipah virus (niv) glycoprotein (g) and canine distemper virus (cdv) haemagglutinin (h) proteins carrying the respective heterologous cytoplasmic domain, as well as a series of m ...201626813519
identifying early target cells of nipah virus infection in syrian hamsters.nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. end stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of nipah virus infection have not been identified. here, we detected the initial target tissues and cells of nipah virus and tracked virus dissemination during the early phase of infection in syrian hamsters inoc ...201627812087
investigating rare risk factors for nipah virus in bangladesh: 2001-2012.human nipah encephalitis outbreaks have been identified almost yearly in bangladesh since 2001. though raw date palm sap consumption and person-to-person contact are recognized as major transmission pathways, alternative pathways of transmission are plausible and may not have been identified due to limited statistical power in each outbreak. we conducted a risk factor analysis using all 157 cases and 632 controls surveyed in previous investigations during 2004-2012 to identify exposures independ ...201627738775
the matrix protein of nipah virus targets the e3-ubiquitin ligase trim6 to inhibit the ikkε kinase-mediated type-i ifn antiviral response.for efficient replication, viruses have developed mechanisms to evade innate immune responses, including the antiviral type-i interferon (ifn-i) system. nipah virus (niv), a highly pathogenic member of the paramyxoviridae family (genus henipavirus), is known to encode for four p gene-derived viral proteins (p/c/w/v) with ifn-i antagonist functions. here we report that niv matrix protein (niv-m), which is important for virus assembly and budding, can also inhibit ifn-i responses. ifn-i production ...201627622505
nucleocytoplasmic trafficking of nipah virus w protein involves multiple discrete interactions with the nuclear import and export machinery.paramyxoviruses replicate in the cytoplasm with no obvious requirement to interact with the nucleus. nevertheless, the w protein of the highly lethal bat-borne paramyxovirus nipah virus (niv) is known to undergo specific targeting to the nucleus, mediated by a single nuclear localisation signal (nls) within the c-terminal domain. here, we report for the first time that additional sites modulate nucleocytoplasmic localisation of w. we show that the n-terminal domain interacts with importin α1 and ...201627622322
region of nipah virus c protein responsible for shuttling between the cytoplasm and nucleus.nipah virus (niv) causes severe encephalitis in humans, with high mortality. niv nonstructural c protein (niv-c) is essential for its pathogenicity, but its functions are unclear. in this study, we focused on niv-c trafficking in cells and found that it localizes predominantly in the cytoplasm but partly in the nucleus. an analysis of niv-c mutants showed that amino acids 2, 21-24 and 110-139 of niv-c are important for its localization in the cytoplasm. inhibitor treatment indicates that the nuc ...201627501340
roles of nuclear trafficking in infection by cytoplasmic negative-strand rna viruses: paramyxoviruses and beyond.genome replication and virion production by most negative-sense rna viruses (nsvs) occurs exclusively in the cytoplasm, but many nsv-expressed proteins undergo active nucleocytoplasmic trafficking via signals that exploit cellular nuclear transport pathways. nuclear trafficking has been reported both for nsv accessory proteins (including isoforms of the rabies virus phosphoprotein, and v, w and c proteins of paramyxoviruses) and for structural proteins. trafficking of the former is thought to en ...201627498841
it's not only what you say, it's also how you say it: communicating nipah virus prevention messages during an outbreak in bangladesh.during a fatal nipah virus (niv) outbreak in bangladesh, residents rejected biomedical explanations of niv transmission and treatment and lost trust in the public healthcare system. field anthropologists developed and communicated a prevention strategy to bridge the gap between the biomedical and local explanation of the outbreak.201627495927
pathogenic differences between nipah virus bangladesh and malaysia strains in primates: implications for antibody therapy.nipah virus (niv) is a paramyxovirus that causes severe disease in humans and animals. there are two distinct strains of niv, malaysia (nivm) and bangladesh (nivb). differences in transmission patterns and mortality rates suggest that nivb may be more pathogenic than nivm. to investigate pathogenic differences between strains, 4 african green monkeys (agm) were exposed to nivm and 4 agms were exposed to nivb. while nivb was uniformly lethal, only 50% of nivm-infected animals succumbed to infecti ...201627484128
molecular epidemiology and phylogeny of nipah virus infection: a mini review.nipah virus (niv) is a member of the genus henipavirus of the family paramyxoviridae, characterized by high pathogenicity and endemic in south asia. it is classified as a biosafety level-4 (bsl-4) agent. the case-fatality varies from 40% to 70% depending on the severity of the disease and on the availability of adequate healthcare facilities. at present no antiviral drugs are available for niv disease and the treatment is just supportive. phylogenetic and evolutionary analyses can be used to hel ...201627393089
nipah virus matrix protein: expert hacker of cellular machines.nipah virus (niv, henipavirus) is a highly lethal emergent zoonotic paramyxovirus responsible for repeated human outbreaks of encephalitis in south east asia. there are no approved vaccines or treatments, thus improved understanding of niv biology is imperative. niv matrix protein recruits a plethora of cellular machinery to scaffold and coordinate virion budding. intriguingly, matrix also hijacks cellular trafficking and ubiquitination pathways to facilitate transient nuclear localization. whil ...201627350027
the nature of exposure drives transmission of nipah viruses from malaysia and bangladesh in ferrets.person-to-person transmission is a key feature of human nipah virus outbreaks in bangladesh. in contrast, in an outbreak of nipah virus in malaysia, people acquired infections from pigs. it is not known whether this important epidemiological difference is driven primarily by differences between niv bangladesh (niv-bd) and malaysia (niv-my) at a virus level, or by environmental or host factors. in a time course study, ferrets were oronasally exposed to equivalent doses of niv-bd or niv-my. more r ...201627341030
eukaryotic elongation factor 1-beta interacts with the 5' untranslated region of the m gene of nipah virus to promote mrna translation.nipah virus belongs to the genus henipavirus in the family paramyxoviridae, and its rna genome is larger than those of other paramyxoviruses because it has long untranslated regions (utrs) in each gene. however, the functions of these utrs are not fully understood. in this study, we investigated the functions of the 5' utrs and found that the 5' utr of the m gene upregulated the translation of a reporter gene. using an rna pull-down assay, we showed that eukaryotic elongation factor 1-beta (eef1 ...201627236461
nipah virus c protein recruits tsg101 to promote the efficient release of virus in an escrt-dependent pathway.the budding of nipah virus, a deadly member of the henipavirus genus within the paramyxoviridae, has been thought to be independent of the host escrt pathway, which is critical for the budding of many enveloped viruses. this conclusion was based on the budding properties of the virus matrix protein in the absence of other virus components. here, we find that the virus c protein, which was previously investigated for its role in antagonism of innate immunity, recruits the escrt pathway to promote ...201627203423
hsp90 chaperoning in addition to phosphoprotein required for folding but not for supporting enzymatic activities of measles and nipah virus l polymerases.nonsegmented negative-stranded rna viruses, or members of the order mononegavirales, share a conserved gene order and the use of elaborate transcription and replication machinery made up of at least four molecular partners. these partners have coevolved with the acquisition of the permanent encapsidation of the entire genome by the nucleoprotein (n) and the use of this n-rna complex as a template for the viral polymerase composed of the phosphoprotein (p) and the large enzymatic protein (l). not ...201627170753
nipah virus c and w proteins contribute to respiratory disease in ferrets.nipah virus (niv) is a highly lethal paramyxovirus that recently emerged as a causative agent of febrile encephalitis and severe respiratory disease in humans. the ferret model has emerged as the preferred small-animal model with which to study niv disease, but much is still unknown about the viral determinants of niv pathogenesis, including the contribution of the c protein in ferrets. additionally, studies have yet to examine the synergistic effects of the various p gene products on pathogenes ...201627147733
species-specific and individual differences in nipah virus replication in porcine and human airway epithelial cells.highly pathogenic nipah virus (niv) causes symptomatic infections in pigs and humans. the severity of respiratory symptoms is much more pronounced in pigs than in humans, suggesting species-specific differences of niv replication in porcine and human airways. here, we present a comparative study on productive niv replication in primary airway epithelial cell cultures of the two species. we reveal that niv growth substantially differs in primary cells between pigs and humans, with a more rapid sp ...201627075405
molecular characterization of nipah virus from pteropus hypomelanus in southern thailand.nipah virus (niv) first emerged in malaysia in 1998, with two bat species (pteropus hypomelanus and p. vampyrus) as the putative natural reservoirs. in 2002, niv igg antibodies were detected in these species from thailand, but viral rna could not be detected for strain characterization. two strains of niv (malaysia and bangladesh) have been found in p. lylei in central thailand, although bangladesh strain, the causative strain for the outbreak in bangladesh since 2001, was dominant. to understan ...201627016237
nipah virus transmission from bats to humans associated with drinking traditional liquor made from date palm sap, bangladesh, 2011-2014.nipah virus (niv) is a paramyxovirus, and pteropus spp. bats are the natural reservoir. from december 2010 through march 2014, hospital-based encephalitis surveillance in bangladesh identified 18 clusters of niv infection. the source of infection for case-patients in 3 clusters in 2 districts was unknown. a team of epidemiologists and anthropologists investigated these 3 clusters comprising 14 case-patients, 8 of whom died. among the 14 case-patients, 8 drank fermented date palm sap (tari) regul ...201626981928
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