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characterization of african bat henipavirus gh-m74a glycoproteins.in recent years, novel henipavirus-related sequences have been identified in bats in africa. to evaluate the potential of african bat henipaviruses to spread in non-bat mammalian cells, we compared the biological functions of the surface glycoproteins g and f of the prototype african henipavirus gh-m74a with those of the glycoproteins of nipah virus (niv), a well-characterized pathogenic member of the henipavirus genus. glycoproteins are central determinants for virus tropism, as efficient bindi ...201424296468
the role of landscape composition and configuration on pteropus giganteus roosting ecology and nipah virus spillover risk in bangladesh.nipah virus has caused recurring outbreaks in central and northwest bangladesh (the "nipah belt"). little is known about roosting behavior of the fruit bat reservoir, pteropus giganteus, or factors driving spillover. we compared human population density and ecological characteristics of case villages and control villages (no reported outbreaks) to understand their role in p. giganteus roosting ecology and nipah virus spillover risk. nipah belt villages have a higher human population density (p < ...201424323516
single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal nipah virus disease.nipah virus (niv) is a highly pathogenic zoonotic agent in the family paramyxoviridae that is maintained in nature by bats. outbreaks have occurred in malaysia, singapore, india, and bangladesh and have been associated with 40 to 75% case fatality rates. there are currently no vaccines or postexposure treatments licensed for combating human niv infection.201324330654
nipah virus infection: current scenario.the emergence of nipah virus (niv) infection into the pig population and subsequently into the human population is believed to be due to changes in ecological conditions. in malaysia, a major niv outbreak occurred in pigs and humans from september 1998 to april 1999 that resulted in infection of 265 and death of 105 persons. about 1.1 million pigs had to be destroyed to control the outbreak. the disease was recorded in the form of a major outbreak in india in 2001 and then a small incidence in 2 ...201324426305
surface glycoproteins of the recently identified african henipavirus promote viral entry and cell fusion in a range of human, simian and bat cell lines.the recent discovery of a wide range of henipavirus-like viruses circulating in megabats in africa raises the question as to the zoonotic potential of these pathogens given the high human mortality rates seen with their pathogenic relatives nipah virus and hendra virus. in the absence of cultured infectious african henipavirus we have performed experiments with recombinant f and g glycoproteins from the representative african henipavirus strain m74a aimed at estimating its cellular tropism and c ...201424452140
identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and ebola, hendra, and nipah viruses by using a novel high-throughput screening assay.severe acute respiratory syndrome coronavirus (sars-cov) and ebola, hendra, and nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. these viruses depend on cathepsin l for entry into their target cells. the viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. in this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoprot ...201424501399
activation of paramyxovirus membrane fusion and virus entry.the paramyxoviruses represent a diverse virus family responsible for a wide range of human and animal diseases. in contrast to other viruses, such as hiv and influenza virus, which use a single glycoprotein to mediate host receptor binding and virus entry, the paramyxoviruses require two distinct proteins. one of these is an attachment glycoprotein that binds receptor, while the second is a fusion glycoprotein, which undergoes conformational changes that drive virus-cell membrane fusion and viru ...201424530984
assessing the risk of nipah virus establishment in australian flying-foxes.nipah virus (niv) is a recently emerged zoonotic virus that causes severe disease in humans. the reservoir hosts for niv, bats of the genus pteropus (known as flying-foxes) are found across the asia-pacific including australia. while niv has not been detected in australia, evidence for niv infection has been found in flying-foxes in some of australia's closest neighbours. a qualitative risk assessment was undertaken to assess the risk of niv establishing in australian flying-foxes through flying ...201524580962
evolution and structural organization of the c proteins of paramyxovirinae.the phosphoprotein (p) gene of most paramyxovirinae encodes several proteins in overlapping frames: p and v, which share a common n-terminus (pnt), and c, which overlaps pnt. overlapping genes are of particular interest because they encode proteins originated de novo, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. the c proteins cluster in three groups, comprising measles, nipah, and sendai virus. we predic ...201424587180
discerning intersecting fusion-activation pathways in the nipah virus using machine learning.the fusion of nipah with host cells is facilitated by two of their glycoproteins, the g and the f proteins. the binding of cellular ephrins to the g head domain causes the g stalk domain to interact differently with f, which activates f to mediate virus-host fusion. to gain insight into how the ephrin-binding signal transduces from the head to the stalk domain of g, we examine quantitatively the differences between the conformational ensembles of the g head domain in its ephrin-bound and unbound ...201424615845
foodborne transmission of nipah virus in syrian hamsters.since 2001, outbreaks of nipah virus have occurred almost every year in bangladesh with high case-fatality rates. epidemiological data suggest that in bangladesh, nipah virus is transmitted from the natural reservoir, fruit bats, to humans via consumption of date palm sap contaminated by bats, with subsequent human-to-human transmission. to experimentally investigate this epidemiological association between drinking of date palm sap and human cases of nipah virus infection, we determined the via ...201424626480
single-dose live-attenuated nipah virus vaccines confer complete protection by eliciting antibodies directed against surface glycoproteins.nipah virus (niv), a zoonotic pathogen causing severe respiratory illness and encephalitis in humans, emerged in malaysia in 1998 with subsequent outbreaks on an almost annual basis since 2001 in parts of the indian subcontinent. the high case fatality rate, human-to-human transmission, wide-ranging reservoir distribution and lack of licensed intervention options are making niv a serious regional and potential global public health problem. the objective of this study was to develop a fast-acting ...201424631094
evaluation of luciferase and gfp-expressing nipah viruses for rapid quantitative antiviral screening.nipah virus (niv) outbreaks have occurred in malaysia, india, and bangladesh, and the virus continues to cause annual outbreaks of fatal human encephalitis in bangladesh due to spillover from its bat host reservoir. due to its high pathogenicity, its potential use for bio/agro-terrorism, and to the current lack of approved therapeutics, niv is designated as an overlap select agent requiring biosafety level-4 containment. although the development of therapeutic monoclonal antibodies and soluble p ...201424680955
a human lung xenograft mouse model of nipah virus infection.nipah virus (niv) is a member of the genus henipavirus (family paramyxoviridae) that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%). niv can cause acute lung injury (ali) in humans, and human-to-human transmission has been observed in recent outbreaks of niv. while the exact route of transmission to humans is not known, we have previously shown that niv can efficiently infect human respiratory epithelial cells. the molecular me ...201424699832
a bsl-4 high-throughput screen identifies sulfonamide inhibitors of nipah virus.nipah virus is a biosafety level 4 (bsl-4) pathogen that causes severe respiratory illness and encephalitis in humans. to identify novel small molecules that target nipah virus replication as potential therapeutics, southern research institute and galveston national laboratory jointly developed an automated high-throughput screening platform that is capable of testing 10,000 compounds per day within bsl-4 biocontainment. using this platform, we screened a 10,080-compound library using a cell-bas ...024735442
piloting the promotion of bamboo skirt barriers to prevent nipah virus transmission through date palm sap in bangladesh.drinking raw date palm sap contaminated with infected fruit bat saliva or urine is an important mode of nipah virus transmission to humans in bangladesh. bamboo skirts are an effective way to interrupt bat access to the sap. we conducted a study from november 2008 to march 2009 to explore the effectiveness of higher- and lower-intensity interventions by promoting bamboo skirt preparation and use among sap harvesters (gachhis). we spent 280 person-hours in two villages for the higher-intensity in ...201424755262
[summary of research works on viruses in the vietnam research station, institute of tropical medicine, nagasaki university].institute of tropical medicine, nagasaki university (nekken) and national institute of hygiene and epidemiology, vietnam (nihe) jointly conducted a project from 2006 on emerging and re-emerging infectious diseases (erid) granted by the ministry of education, science, culture and technology (mext) of japan. fifteen independent researches have been carried out by 7 scientists who stationed in the vietnam research station (vrs), and by approximately 60 visiting scientists. a wide variety of viruses ...201324769580
roosting behaviour and habitat selection of pteropus giganteus reveals potential links to nipah virus epidemiology.1. flying foxes pteropus spp. play a key role in forest regeneration as seed dispersers and are also the reservoir of many viruses, including nipah virus in bangladesh. little is known about their habitat requirements, particularly in south asia. identifying pteropus habitat preferences could assist in understanding the risk of zoonotic disease transmission broadly, and in bangladesh, could help explain the spatial distribution of human nipah virus cases. 2. we analysed characteristics of pterop ...201424778457
anp32b is a nuclear target of henipavirus m proteins.membrane envelopment and budding of negative strand rna viruses (nsvs) is mainly driven by viral matrix proteins (m). in addition, several m proteins are also known to be involved in host cell manipulation. knowledge about the cellular targets and detailed molecular mechanisms, however, is poor for many m proteins. for instance, nipah virus (niv) m protein trafficking through the nucleus is essential for virus release, but nuclear targets of niv m remain unknown. to identify cellular interactors ...201424823948
co-assembly of viral envelope glycoproteins regulates their polarized sorting in neurons.newly synthesized envelope glycoproteins of neuroinvasive viruses can be sorted in a polarized manner to the somatodendritic and/or axonal domains of neurons. although critical for transneuronal spread of viruses, the molecular determinants and interregulation of this process are largely unknown. we studied the polarized sorting of the attachment (niv-g) and fusion (niv-f) glycoproteins of nipah virus (niv), a paramyxovirus that causes fatal human encephalitis, in rat hippocampal neurons. when e ...201424831812
potential for introduction of bat-borne zoonotic viruses into the eu: a review.bat-borne viruses can pose a serious threat to human health, with examples including nipah virus (niv) in bangladesh and malaysia, and marburg virus (marv) in africa. to date, significant human outbreaks of such viruses have not been reported in the european union (eu). however, eu countries have strong historical links with many of the countries where niv and marv are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of th ...201424841385
ethical dilemmas in protecting individual rights versus public protection in the case of infectious diseases.infectious diseases-including emerging and re-emerging diseases such as ebola and tuberculosis-continue to be important causes of morbidity and mortality in the globalizing, contemporary world. this article discusses the ethical issues associated with protecting the rights of individuals versus the protection of the health of populations in the case of infectious diseases. the discussion uses the traditional medical ethics approach together with the public health approach presented by faden and ...201324847171
virus particle release from glycosphingolipid-enriched microdomains is essential for dendritic cell-mediated capture and transfer of hiv-1 and henipavirus.human immunodeficiency virus type 1 (hiv-1) exploits dendritic cells (dcs) to promote its transmission to t cells. we recently reported that the capture of hiv-1 by mature dendritic cells (mdcs) is mediated by an interaction between the glycosphingolipid (gsl) gm3 on virus particles and cd169/siglec-1 on mdcs. since hiv-1 preferentially buds from gsl-enriched lipid microdomains on the plasma membrane, we hypothesized that the virus assembly and budding site determines the ability of hiv-1 to int ...201424872578
subclinical infection without encephalitis in mice following intranasal exposure to nipah virus-malaysia and nipah virus-bangladesh.nipah virus and hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. in humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. recently we reported a wild-type mouse model of hendra virus (hev) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disea ...201424890603
therapeutic treatment of nipah virus infection in nonhuman primates with a neutralizing human monoclonal antibody.nipah virus (niv) is an emerging zoonotic paramyxovirus that causes severe and often fatal disease in pigs and humans. there are currently no vaccines or treatments approved for human use. studies in small-animal models of niv infection suggest that antibody therapy may be a promising treatment. however, most studies have assessed treatment at times shortly after virus exposure before animals show signs of disease. we assessed the efficacy of a fully human monoclonal antibody, m102.4, at several ...201424964990
antagonism of the phosphatase pp1 by the measles virus v protein is required for innate immune escape of mda5.the cytosolic sensor mda5 is crucial for antiviral innate immune defense against various rna viruses including measles virus; as such, many viruses have evolved strategies to antagonize the antiviral activity of mda5. here, we show that measles virus escapes mda5 detection by targeting the phosphatases pp1α and pp1γ, which regulate mda5 activity by removing an inhibitory phosphorylation mark. the v proteins of measles virus and the related paramyxovirus nipah virus interact with pp1α/γ, preventi ...025011105
henipavirus encephalitis. 201425015510
attachment protein g of an african bat henipavirus is differentially restricted in chiropteran and nonchiropteran cells.henipaviruses are associated with pteropodid reservoir hosts. the glycoproteins g and f of an african henipavirus (strain m74) have been reported to induce syncytium formation in kidney cells derived from a hypsignathus monstrosus bat (hypni/1.1) but not in nonchiropteran bhk-21 and vero76 cells. here, we show that syncytia are also induced in two other pteropodid cell lines from hypsignathus monstrosus and eidolon helvum bats upon coexpression of the m74 glycoproteins. the g protein was transpo ...201425100832
structure of nipah virus unassembled nucleoprotein in complex with its viral chaperone.nipah virus (niv) is a highly pathogenic emergent paramyxovirus causing deadly encephalitis in humans. its replication requires a constant supply of unassembled nucleoprotein (n(0)) in complex with its viral chaperone, the phosphoprotein (p). to elucidate the chaperone function of p, we reconstituted niv the n(0)-p core complex and determined its crystal structure. the binding of the n-terminal region of p blocks the polymerization of n by interfering with subdomain exchange between n protomers ...201425108352
methyltransferase-defective avian metapneumovirus vaccines provide complete protection against challenge with the homologous colorado strain and the heterologous minnesota strain.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. since its discovery in the 1970s, ampv has been recognized as an economically important pathogen in the poultry industry worldwide. the conserved region vi (cr vi) of the large (l) polymerase proteins of paramyxoviruses catalyzes methyltransferase (mtase) activities that typically methylate viral ...201425122790
european bats as carriers of viruses with zoonotic potential.bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (marburg virus, nipah virus, hendra virus, rabies virus, and coronaviruses). while numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in european bats. although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are con ...201425123684
prediction of epitope-based peptides for the utility of vaccine development from fusion and glycoprotein of nipah virus using in silico approach.this study aims to design epitope-based peptides for the utility of vaccine development by targeting glycoprotein g and envelope protein f of nipah virus (niv) that, respectively, facilitate attachment and fusion of niv with host cells. using various databases and tools, immune parameters of conserved sequence(s) from g and f proteins of different isolates of niv were tested to predict probable epitope(s). binding analyses of the peptides with mhc class-i and class-ii molecules, epitope conserva ...201425147564
matrix proteins of nipah and hendra viruses interact with beta subunits of ap-3 complexes.paramyxoviruses and other negative-strand rna viruses encode matrix proteins that coordinate the virus assembly process. the matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. using a co-affinity purification strategy, we have identified the beta subunit of the ap-3 adapter protein complex, ap3b1, as a binding partner for the m proteins of the zoonotic paramyxoviruses nipah v ...201425210190
animal models of disease shed light on nipah virus pathogenesis and transmission.nipah virus is an emerging virus infection that causes yearly disease outbreaks with high case fatality rates in bangladesh. nipah virus causes encephalitis and systemic vasculitis, sometimes in combination with respiratory disease. pteropus species fruit bats are the natural reservoir of nipah virus and zoonotic transmission can occur directly or via an intermediate host; human-to-human transmission occurs regularly. in this review we discuss the current state of knowledge on the pathogenesis a ...201525229234
effect of galectins on viral transmission.recent reports suggest that some galectins bind to enveloped viruses. they include influenza virus, human immunodeficiency virus-1 (hiv-1), human t-cell leukemia virus-1 (htlv-1), and nipah virus. it is also suggested that the interaction between viruses and galectins influences viral attachment to their susceptible cells, affecting the viral infectivity. our work suggests that galectin-1 increases the infectivity of hiv-1 and htvl-1. indeed, galectin-1 promotes the initial adsorption of hiv-1 t ...201525253155
from risk analysis to risk governance - adapting to an ever more complex future.risk analysis is now widely accepted amongst veterinary authorities and other stakeholders around the world as a conceptual framework for integrating scientific evidence into animal health decision making. the resulting risk management for most diseases primarily involves linking epidemiological understanding with diagnostics and/or vaccines. recent disease outbreaks such as nipah virus, sars, avian influenza h5n1, bluetongue serotype 8 and schmallenberg virus have led to realising that we need ...201425273958
nipah virion entry kinetics, composition, and conformational changes determined by enzymatic virus-like particles and new flow virometry tools.virus-cell membrane fusion is essential for enveloped virus infections. however, mechanistic viral membrane fusion studies have predominantly focused on cell-cell fusion models, largely due to the low availability of technologies capable of characterizing actual virus-cell membrane fusion. although cell-cell fusion assays are valuable, they do not fully recapitulate all the variables of virus-cell membrane fusion. drastic differences between viral and cellular membrane lipid and protein composit ...201425275126
rhabdovirus-based vaccine platforms against henipaviruses.the emerging zoonotic pathogens hendra virus (hev) and nipah virus (niv) are in the genus henipavirus in the family paramyxoviridae. hev and niv infections can be highly fatal to humans and livestock. the goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (rabv) and recombinant vesicular stomatitis virus (vsv), expressing either the codon-optimized or the wild-type (wt) hev glyco ...201525320306
integrated cluster- and case-based surveillance for detecting stage iii zoonotic pathogens: an example of nipah virus surveillance in bangladesh.this paper explores the utility of cluster- and case-based surveillance established in government hospitals in bangladesh to detect nipah virus, a stage iii zoonotic pathogen. physicians listed meningo-encephalitis cases in the 10 surveillance hospitals and identified a cluster when ⩾2 cases who lived within 30 min walking distance of one another developed symptoms within 3 weeks of each other. physicians collected blood samples from the clustered cases. as part of case-based surveillance, blood ...201525342551
syrian hamsters (mesocricetus auratus) oronasally inoculated with a nipah virus isolate from bangladesh or malaysia develop similar respiratory tract lesions.nipah virus is a paramyxovirus in the genus henipavirus, which has caused outbreaks in humans in malaysia, india, singapore, and bangladesh. whereas the human cases in malaysia were characterized mainly by neurological symptoms and a case fatality rate of ∼40%, cases in bangladesh also exhibited respiratory disease and had a case fatality rate of ∼70%. here, we compared the histopathologic changes in the respiratory tract of syrian hamsters, a well-established small animal disease model for nipa ...201525352203
mission critical: mobilization of essential animal models for ebola, nipah, and machupo virus infections.the reports for ebola virus zaire (ebov), nipah virus, and machupo virus (macv) pathogenesis, in this issue of veterinary pathology, are timely considering recent events, both nationally and internationally. ebov, nipah virus, and macv cause highly lethal infections for which no food and drug administration (fda) licensed vaccines or therapies exist. not only are there concerns that these agents could be used by those with malicious intent, but shifts in ecological distribution of viral reservoi ...201525352204
a novel factor i activity in nipah virus inhibits human complement pathways through cleavage of c3b.complement is an innate immune system that most animal viruses must face during natural infections. given that replication and dissemination of the highly pathogenic nipah virus (niv) include exposure to environments rich in complement factors, we tested the in vitro sensitivity of niv to complement-mediated neutralization. here we show that niv was completely resistant to in vitro neutralization by normal human serum (nhs). treatment of purified niv with nhs activated complement pathways, but t ...201425355897
viruses and disease: emerging concepts for prevention, diagnosis and treatment.viruses cause a wide range of human diseases, ranging from acute self-resolving conditions to acute fatal diseases. effects that arise long after the primary infection can also increase the propensity for chronic conditions or lead to the development of cancer. recent advances in the fields of virology and pathology have been fundamental in improving our understanding of viral pathogenesis, in providing improved vaccination strategies and in developing newer, more effective treatments for patien ...201525366544
efficient reverse genetics reveals genetic determinants of budding and fusogenic differences between nipah and hendra viruses and enables real-time monitoring of viral spread in small animal models of henipavirus infection.nipah virus (niv) and hendra virus (hev) are closely related henipaviruses of the paramyxovirinae. spillover from their fruit bat reservoirs can cause severe disease in humans and livestock. despite their high sequence similarity, niv and hev exhibit apparent differences in receptor and tissue tropism, envelope-mediated fusogenicity, replicative fitness, and other pathophysiologic manifestations. to investigate the molecular basis for these differences, we first established a highly efficient re ...201525392218
ecological dynamics of emerging bat virus spillover.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 ho ...201525392474
evidence for henipavirus spillover into human populations in africa.zoonotic transmission of lethal henipaviruses (hnvs) from their natural fruit bat reservoirs to humans has only been reported in australia and south/southeast asia. however, a recent study discovered numerous hnv clades in african bat samples. to determine the potential for hnv spillover events among humans in africa, here we examine well-curated sets of bat (eidolon helvum, n = 44) and human (n = 497) serum samples from cameroon for nipah virus (niv) cross-neutralizing antibodies (niv-x-nabs). ...201425405640
serological evidence of henipavirus exposure in cattle, goats and pigs in bangladesh.nipah virus (niv) is an emerging disease that causes severe encephalitis and respiratory illness in humans. pigs were identified as an intermediate host for niv transmission in malaysia. in bangladesh, niv has caused recognized human outbreaks since 2001 and three outbreak investigations identified an epidemiological association between close contact with sick or dead animals and human illness.201425412358
bibliography of clinical research in malaysia: methods and brief results.this article describes the methodology of this bibliography. a search was conducted on the following: (1) bibliographic databases (pubmed, scopus, and other databases) using search terms that maximize the retrieval of malaysian publications; (2) individual journal search of malaysian healthrelated journals; (3) a targeted search of google and google scholar; (4) searching of malaysian institutional repositories; (5) searching of ministry of health and clinical research centre website. the public ...201425417946
nipah encephalitis - an update.between september 1998 to may 1999, malaysia and singapore were hit by an outbreak of fatal encephalitis caused by a novel virus from the paramyxovirus family. this virus was subsequently named as nipah virus, after the sungei nipah village in negeri sembilan, where the virus was first isolated. the means of transmission was thought to be from bats-topigs and subsequently pigs-to-human. since 2001, almost yearly outbreak of nipah encephalitis has been reported from bangladesh and west bengal, in ...201425417957
water dynamics at protein-protein interfaces: molecular dynamics study of virus-host receptor complexes.the dynamical properties of water at protein-water interfaces are unlike those in the bulk. here we utilize molecular dynamics simulations to study water dynamics in interstitial regions between two proteins. we consider two natural protein-protein complexes, one in which the nipah virus g protein binds to cellular ephrin b2 and the other in which the same g protein binds to ephrin b3. while the two complexes are structurally similar, the two ephrins share only a modest sequence identity of ∼50% ...201425420132
birth and pathogenesis of rogue respiratory viruses.emerging infectious diseases of zoonotic origin are shaping today's infectious disease field more than ever. in this article, we introduce and review three emerging zoonotic viruses. novel hantaviruses emerged in the americas in the mid-1990s as the cause of severe respiratory infections, designated hantavirus pulmonary syndrome, with case fatality rates of around 40%. nipah virus emerged a few years later, causing respiratory infections and encephalitis in southeast asia, with case fatality rat ...201525423349
nipah virus attachment glycoprotein stalk c-terminal region links receptor binding to fusion triggering.membrane fusion is essential for paramyxovirus entry into target cells and for the cell-cell fusion (syncytia) that results from many paramyxoviral infections. the concerted efforts of two membrane-integral viral proteins, the attachment (hn, h, or g) and fusion (f) glycoproteins, mediate membrane fusion. the emergent nipah virus (niv) is a highly pathogenic and deadly zoonotic paramyxovirus. we recently reported that upon cell receptor ephrinb2 or ephrinb3 binding, at least two conformational c ...201525428863
meeting report vlpnpv: session 6: development and characterization. 201425458600
dynamics of the intrinsically disordered c-terminal domain of the nipah virus nucleoprotein and interaction with the x domain of the phosphoprotein as unveiled by nmr spectroscopy.we provide an atomic-resolution description based on nmr spectroscopy, of the intrinsically disordered c-terminal domain of the nipah virus nucleoprotein (ntail ), both in its isolated state and within the nucleocapsid (nc). within the nc the second half of ntail retains conformational behavior similar to that of isolated ntail , whereas the first half of ntail becomes much more rigid. in spite of the mostly disordered nature of ntail , chemical shifts and relaxation measurements show a signific ...201525492314
immunology of bats and their viruses: challenges and opportunities.bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including nipah virus, marburg virus and rabies virus. they also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including sars and mers coronaviruses. as is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic ...201425494448
timing of galectin-1 exposure differentially modulates nipah virus entry and syncytium formation in endothelial cells.nipah virus (niv) is a deadly emerging enveloped paramyxovirus that primarily targets human endothelial cells. endothelial cells express the innate immune effector galectin-1 that we have previously shown can bind to specific n-glycans on the niv envelope fusion glycoprotein (f). niv-f mediates fusion of infected endothelial cells into syncytia, resulting in endothelial disruption and hemorrhage. galectin-1 is an endogenous carbohydrate-binding protein that binds to specific glycans on niv-f to ...201425505064
exposure-based screening for nipah virus encephalitis, bangladesh.we measured the performance of exposure screening questions to identify nipah virus encephalitis in hospitalized encephalitis patients during the 2012-13 nipah virus season in bangladesh. the sensitivity (93%), specificity (82%), positive predictive value (37%), and negative predictive value (99%) results suggested that screening questions could more quickly identify persons with nipah virus encephalitis.201525625615
henipavirus pathogenesis and antiviral approaches.hendra virus and nipah virus are closely related, recently emerged zoonotic paramyxoviruses, belonging to the henipavirus genus. both viruses induce generalized vasculitis affecting particularly the respiratory tract and cns. the exceptionally broad species tropism of henipavirus, the high case fatality rate and person-to-person transmission associated with nipah virus outbreaks emphasize the necessity of effective antiviral strategies for these intriguing threatening pathogens. current therapeu ...201525634624
insights into the coiled-coil organization of the hendra virus phosphoprotein from combined biochemical and saxs studies.nipah and hendra viruses are recently emerged paramyxoviruses belonging to the henipavirus genus. the henipavirus phosphoprotein (p) consists of a large intrinsically disordered domain and a c-terminal domain (pct) containing alternating disordered and ordered regions. among these latter is the p multimerization domain (pmd). using biochemical, analytical ultracentrifugation and small-angle x-ray scattering (saxs) studies, we show that hendra virus (hev) pmd forms an elongated coiled-coil homotr ...201525637789
detailed analysis of the african green monkey model of nipah virus disease.henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. there are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. we performed a comprehensive and statistically-powered evaluation of the african green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. african green m ...201525706617
role of hydrogen sulfide in paramyxovirus infections.hydrogen sulfide (h2s) is an endogenous gaseous mediator that has gained increasing recognition as an important player in modulating acute and chronic inflammatory diseases. however, its role in virus-induced lung inflammation is currently unknown. respiratory syncytial virus (rsv) is a major cause of upper and lower respiratory tract infections in children for which no vaccine or effective treatment is available. using the slow-releasing h2s donor gyy4137 and propargylglycin (pag), an inhibitor ...201525740991
heparan sulfate-dependent enhancement of henipavirus infection.nipah virus and hendra virus are emerging, highly pathogenic, zoonotic paramyxoviruses that belong to the genus henipavirus. they infect humans as well as numerous mammalian species. both viruses use ephrin-b2 and -b3 as cell entry receptors, and following initial entry into an organism, they are capable of rapid spread throughout the host. we have previously reported that nipah virus can use another attachment receptor, different from its entry receptors, to bind to nonpermissive circulating le ...201525759505
[study of pathogenicity of nipah virus and its vaccine development].nipah virus (niv), a paramyxovirus, was first discovered in malaysia in 1998 in an outbreak of infection in pigs and humans, and incurred a high fatality rate in humans. we established a system that enabled the rescue of replicating nivs from a cloned dna. using the system, we analyzed the functions of accessory proteins in infected cells and the implications in in vivo pathogenicity. further, we have developed a recombinant measles virus (rmv) vaccine expressing niv envelope glycoproteins, whic ...201425765986
viral immune surveillance: toward a th17/th9 gate to the central nervous system.viral cellular immune surveillance is a dynamic and fluid system that is driven by finely regulated cellular processes including cytokines and other factors locally in the microenvironment and systemically throughout the body. it is questionable as to what extent the central nervous system (cns) is an immune-privileged organ protected by the blood-brain barrier (bbb). recent evidence suggests converging pathways through which viral infection, and its associated immune surveillance processes, may ...201525780281
evidence for ubiquitin-regulated nuclear and subnuclear trafficking among paramyxovirinae matrix proteins.the paramyxovirus matrix (m) protein is a molecular scaffold required for viral morphogenesis and budding at the plasma membrane. transient nuclear residence of some m proteins hints at non-structural roles. however, little is known regarding the mechanisms that regulate the nuclear sojourn. previously, we found that the nuclear-cytoplasmic trafficking of nipah virus m (niv-m) is a prerequisite for budding, and is regulated by a bipartite nuclear localization signal (nlsbp), a leucine-rich nucle ...201525782006
animal models for some important rna viruses of public health concern in searo countries: viral hemorrhagic fever.viral hemorrhagic fevers (vhfs) are major public health problems in the south-east asia regional (sear) countries. vhfs are a group of illnesses; that are caused by four families of viruses, viz. arenaviridae, bunyaviridae, filoviridae and flaviviridae. all vhfs have common features: they affect several organs and damage the blood vessels. these symptoms are often accompanied by hemorrhage. to understand pathogenesis, genetic and environmental influence that increase the risk of vhfs, efficacy a ...201525815861
molecular recognition of human ephrinb2 cell surface receptor by an emergent african henipavirus.the discovery of african henipaviruses (hnvs) related to pathogenic hendra virus (hev) and nipah virus (niv) from southeast asia and australia presents an open-ended health risk. cell receptor use by emerging african hnvs at the stage of host-cell entry is a key parameter when considering the potential for spillover and infection of human populations. the attachment glycoprotein from a ghanaian bat isolate (ghv-g) exhibits <30% sequence identity with asiatic niv-g/hev-g. here, through functional ...201525825759
single-dose live-attenuated vesicular stomatitis virus-based vaccine protects african green monkeys from nipah virus disease.nipah virus is a zoonotic paramyxovirus that causes severe respiratory and/or encephalitic disease in humans, often resulting in death. it is transmitted from pteropus fruit bats, which serve as the natural reservoir of the virus, and outbreaks occur on an almost annual basis in bangladesh or india. outbreaks are small and sporadic, and several cases of human-to-human transmission have been documented as an important feature of the epidemiology of nipah virus disease. there are no approved count ...201525865472
spatial characterization of colonies of the flying fox bat, a carrier of nipah virus in thailand.a major reservoir of nipah virus is believed to be the flying fox genus pteropus, a fruit bat distributed across many of the world's tropical and sub-tropical areas. the emergence of the virus and its zoonotic transmission to livestock and humans have been linked to losses in the bat's habitat. nipah has been identified in a number of indigenous flying fox populations in thailand. while no evidence of infection in domestic pigs or people has been found to date, pig farming is an active agricultu ...201525880385
neglected tropical diseases among the association of southeast asian nations (asean): overview and update.the ten member states of the association of southeast asian nations (asean) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (ntds). almost 200 million people live in extreme poverty in asean countries, mostly in the low or lower middle-income countries of indonesia, the philippines, myanmar, viet nam, and cambodia, and many of them are affected by at least one ntd. however, ntds are prevalent even among upper mi ...201525880767
controlling nipah virus encephalitis in bangladesh: policy options.nipah virus (niv) encephalitis is endemic in bangladesh, with yearly seasonal outbreaks occurring since 2003. niv has a notable case fatality rate, 75-100 per cent depending on the strain. in bangladesh, primary transmission to humans is believed to be because of consumption of bat-contaminated date palm sap (dps). both the disease and the virus have been investigated extensively, however efforts to implement preventive strategies have met social and cultural challenges. here we present a variet ...201525925087
novel functions of hendra virus g n-glycans and comparisons to nipah virus.hendra virus (hev) and nipah virus (niv) are reportedly the most deadly pathogens within the paramyxoviridae family. these two viruses bind the cellular entry receptors ephrin b2 and/or ephrin b3 via the viral attachment glycoprotein g, and the concerted efforts of g and the viral fusion glycoprotein f result in membrane fusion. membrane fusion is essential for viral entry into host cells and for cell-cell fusion, a hallmark of the disease pathobiology. hev g is heavily n-glycosylated, but the f ...201525948743
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
transcriptome profiling of the virus-induced innate immune response in pteropus vampyrus and its attenuation by nipah virus interferon antagonist functions.bats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. as the innate immune response is critical for controlling viruses, the nature of this response in bats and how it may differ from that in other mammals are of great interest. using next-generation transcriptome sequencing (mrna-seq), we profiled the transcriptional response of pteropus vampyrus bat kidney (pvk) cells to newcastle disease virus (ndv), an avian ...201525972557
bats as reservoirs of severe emerging infectious diseases.in recent years severe infectious diseases have been constantly emerging, causing panic in the world. now we know that many of these terrible diseases are caused by viruses originated from bats (table 1), such as ebola virus, marburg, sars coronavirus (sars-cov), mers coronavirus (mers-cov), nipah virus (niv) and hendra virus (hev). these viruses have co-evolved with bats due to bats' special social, biological and immunological features. although bats are not in close contact with humans, spill ...201525997928
receptor-binding domains of spike proteins of emerging or re-emerging viruses as targets for development of antiviral vaccines.a number of emerging and re-emerging viruses have caused epidemics or pandemics of infectious diseases leading to major devastations throughout human history. therefore, developing effective and safe vaccines against these viruses is clearly important for the protection of at-risk populations. our previous studies have shown that the receptor-binding domain (rbd) in the spike protein of severe acute respiratory syndrome (sars)-associated coronavirus (sars-cov) is a key target for the development ...201226038424
nipah virus fusion protein: importance of the cytoplasmic tail for endosomal trafficking and bioactivity.nipah virus (niv) is a highly pathogenic paramyxovirus which encodes two surface glycoproteins: the receptor-binding protein g and the fusion protein f. as for all paramyxoviruses, proteolytic activation of the niv-f protein is an indispensable prerequisite for viral infectivity. interestingly, proteolytic activation of niv-f differs principally from other paramyxoviruses with respect to protease usage (cathepsins instead of trypsin- or furin-like proteases), and the subcellular localization whe ...201526059400
public health disease surveillance networks.zoonotic infections are important sources of human disease; most known emerging infections are zoonotic (e.g., hiv, ebola virus, severe acute respiratory syndrome, nipah virus, and enteropathogenic escherichia coli) and originated as natural infections of other species that acquired opportunities to come in contact with humans. there are also serious infectious diseases classically considered zoonotic, such as influenza, rabies, bubonic plague, brucellosis, and leptospirosis. more recently, it h ...201426082122
the immunomodulating v and w proteins of nipah virus determine disease course.the viral determinants that contribute to nipah virus (niv)-mediated disease are poorly understood compared with other paramyxoviruses. here we use recombinant nivs (rnivs) to examine the contributions of the niv v and w proteins to niv pathogenesis in a ferret model. we show that a v-deficient rniv is susceptible to the innate immune response in vitro and behaves as a replicating non-lethal virus in vivo. remarkably, rniv lacking w expression results in a delayed and altered disease course with ...201526105519
evolving epidemiology of nipah virus infection in bangladesh: evidence from outbreaks during 2010-2011.drinking raw date palm sap is the primary route of nipah virus (niv) transmission from bats to people in bangladesh; subsequent person-to-person transmission is common. during december 2010 to march 2011, we investigated niv epidemiology by interviewing cases using structured questionnaires, in-depth interviews, and group discussions to collect clinical and exposure histories. we conducted a case-control study to identify risk factors for transmission. we identified 43 cases; 23 were laboratory- ...201626122675
a computational approach for designing a universal epitope-based peptide vaccine against nipah virus.nipah virus (niv) is highly pathogenic single-stranded negative sense rna virus. it can cause severe encephalitis and respiratory disease in humans. in addition, niv infects a large range of host including mammals. as a result of its higher zoonotic potential and pathogenicity for human, it has been rated as an alert in recent days. a therapeutic treatment or vaccines has become elusive to fight against this virus. in this study, the attachment (g) and fusion (f) glycoproteins of niv, responsibl ...201526156209
mapping the risk of nipah virus spillover into human populations in south and southeast asia.nipah virus (niv) is a significant emerging zoonotic pathogen given its wide geographic distribution, and the severe morbidity and high mortality that accompanies infection. moreover, the layered landscape epidemiology surrounding spillover from reservoir host species to humans is ill-defined. identifying landscape features that contribute to niv spillover would likely prove helpful in preventing emergence in human populations.201526179654
structural characterization by transmission electron microscopy and immunoreactivity of recombinant hendra virus nucleocapsid protein expressed and purified from escherichia coli.hendra virus (family paramyxoviridae) is a negative sense single-stranded rna virus (nsrv) which has been found to cause disease in humans, horses, and experimentally in other animals, e.g. pigs and cats. pteropid bats commonly known as flying foxes have been identified as the natural host reservoir. the hendra virus nucleocapsid protein (hev n) represents the most abundant viral protein produced by the host cell, and is highly immunogenic with naturally infected humans and horses producing spec ...201526196500
origin and evolution of nipah virus.nipah virus, member of the paramyxoviridae family, is classified as a biosafety level-4 agent and category c priority pathogen. nipah virus disease is endemic in south asia and outbreaks have been reported in malaysia, singapore, india, and bangladesh. bats of the genus pteropus appear to be the natural reservoir of this virus. the aim of this study was to investigate the genetic diversity of nipah virus, to estimate the date of origin and the spread of the infection. the mean value of nipah vir ...201626252523
henipavirus encephalitis: recent developments and advances.the genus henipavirus within the family paramyxoviridae includes the hendra virus (hev) and nipah virus (niv) which were discovered in the 1990s in australia and malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. while hev is confined to australia, more recent niv outbreaks have been reported in bangladesh, india and the philippines. the clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute enc ...201526276024
oxidative stress in nipah virus-infected human small airway epithelial cells.nipah virus (niv) is a zoonotic emerging pathogen that can cause severe and often fatal respiratory disease in humans. the pathogenesis of niv infection of the human respiratory tract remains unknown. reactive oxygen species (ros) produced by airway epithelial cells in response to viral infections contribute to lung injury by inducing inflammation and oxidative stress; however, the role of ros in niv-induced respiratory disease is unknown. to investigate whether niv induces oxidative stress in h ...201526297489
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
regulation of viral rna synthesis by the v protein of parainfluenza virus 5.paramyxoviruses include many important animal and human pathogens. the genome of parainfluenza virus 5 (piv5), a prototypical paramyxovirus, encodes a v protein that inhibits viral rna synthesis. in this work, the mechanism of inhibition was investigated. using mutational analysis and a minigenome system, we identified regions in the n and c termini of the v protein that inhibit viral rna synthesis: one at the very n terminus of v and the second at the c terminus of v. furthermore, we determined ...201526378167
order and disorder in the replicative complex of paramyxoviruses.in this review we summarize available data showing the abundance of structural disorder within the nucleoprotein (n) and phosphoprotein (p) from three paramyxoviruses, namely the measles (mev), nipah (niv) and hendra (hev) viruses. we provide a detailed description of the molecular mechanisms that govern the disorder-to-order transition that the intrinsically disordered c-terminal domain (ntail) of their n proteins undergoes upon binding to the c-terminal x domain (xd) of the homologous p protei ...201526387109
development of a taqman array card for acute-febrile-illness outbreak investigation and surveillance of emerging pathogens, including ebola virus.acute febrile illness (afi) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. we developed a real-time pcr-based taqman array card (tac) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 afi-associated organisms, including 15 viruses (chikungunya, crime ...201526491176
expression and purification of the matrix protein of nipah virus in baculovirus insect cell system.nipah virus (niv) causes fatal respiratory illness and encephalitis in humans and animals. the matrix (m) protein of niv plays an important role in the viral assembly and budding process. thus, an access to the niv m protein is vital to the design of viral antigens as diagnostic reagents. in this study, recombinant dna technology was successfully adopted in the cloning and expression of niv m protein. a recombinant expression cassette (baculovirus expression vector) was used to encode an n-termi ...201626519022
the non-pathogenic henipavirus cedar paramyxovirus phosphoprotein has a compromised ability to target stat1 and stat2.immune evasion by the lethal henipaviruses, hendra (hev) and nipah virus, is mediated by its interferon (ifn) antagonist p gene products, phosphoprotein (p), and the related v and w proteins, which can target the signal transducer and activator of transcription 1 (stat1) and stat2 proteins to inhibit ifn/stat signaling. however, it is not clear if the recently identified non-pathogenic henipavirus, cedar paramyxovirus (cedpv), is also able to antagonize the stat proteins. we performed comparativ ...201526526590
raw sap consumption habits and its association with knowledge of nipah virus in two endemic districts in bangladesh.human nipah virus (niv) infection in bangladesh is a fatal disease that can be transmitted from bats to humans who drink contaminated raw date palm sap collected overnight during the cold season. our study aimed to understand date palm sap consumption habits of rural residents and factors associated with consumption. in november-december 2012 the field team interviewed adult respondents from randomly selected villages from rajbari and kushtia districts in bangladesh. we calculated the proportion ...201526551202
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
crystal structure of the pre-fusion nipah virus fusion glycoprotein reveals a novel hexamer-of-trimers assembly.nipah virus (niv) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. the g glycoprotein attaches to cell receptors, triggering the fusion (f) glycoprotein to execute membrane fusion. here we report the first crystal structure of the pre-fusion form of the niv-f glycoprotein ectodomain. interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. electron tomography of nipah virus-like particles supported the hex ...201526646856
targeting innate immunity for antiviral therapy through small molecule agonists of the rlr pathway.the cellular response to virus infection is initiated when pathogen recognition receptors (prr) engage viral pathogen-associated molecular patterns (pamps). this process results in induction of downstream signaling pathways that activate the transcription factor interferon regulatory factor 3 (irf3). irf3 plays a critical role in antiviral immunity to drive the expression of innate immune response genes, including those encoding antiviral factors, type 1 interferon, and immune modulatory cytokin ...201526676770
nipah virus matrix protein influences fusogenicity and is essential for particle infectivity and stability.nipah virus (niv) causes fatal encephalitic infections in humans. to characterize the role of the matrix (m) protein in the viral life cycle, we generated a reverse genetics system based on niv strain malaysia. using an enhanced green fluorescent protein (egfp)-expressing m protein-deleted niv, we observed a slightly increased cell-cell fusion, slow replication kinetics, and significantly reduced peak titers compared to the parental virus. while increased amounts of viral proteins were found in ...201526676785
early activation of primary brain microvascular endothelial cells by nipah virus glycoprotein-containing particles.nipah virus (niv) is a highly pathogenic paramyxovirus that causes pronounced infection of brain endothelia and central nervous system (cns) inflammation. using primary porcine brain microvascular endothelial cells, we showed that upregulation of e-selectin precedes cytokine induction and is induced not only by infectious niv but also by niv-glycoprotein-containing virus-like particles. this demonstrates that very early events in niv brain endothelial infection do not depend on niv replication b ...201526676791
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
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
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