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The paramyxovirus fusion (F) protein C-terminal region: mutagenesis indicates an indivisible protein unit.Paramyxoviruses enter host cells by fusing the viral envelope with a host cell membrane. Fusion is mediated by the viral fusion (F) protein and it undergoes large irreversible conformational changes to cause membrane merger. The C-terminus of PIV5 F contains a membrane-proximal 7-residue external region (MPER), followed by the transmembrane (TM) domain and a 20-residue cytoplasmic tail. To study the sequence requirements of the F protein C-terminus for fusion, we constructed chimeras containing ...201122171273
antibodies to henipavirus or henipa-like viruses in domestic pigs in ghana, west africa.henipaviruses, hendra virus (hev) and nipah virus (niv), have pteropid bats as their known natural reservoirs. antibodies against henipaviruses have been found in eidolon helvum, an old world fruit bat species, and henipavirus-like nucleic acid has been detected in faecal samples from e. helvum in ghana. the initial outbreak of niv in malaysia led to over 265 human encephalitis cases, including 105 deaths, with infected pigs acting as amplifier hosts for niv during the outbreak. we detected non- ...201121966471
spring-loaded model revisited: paramyxovirus fusion requires engagement of a receptor binding protein beyond initial triggering of the fusion protein.during paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (f), leading to fusion between the viral and cell membranes. according to the existing paradigm of paramyxovirus membrane fusion, the initial activation of f by the receptor binding protein sets off a spring-loaded mechanism whereby the f protein progresses independently through the subsequent steps in the fusion process, ending in membr ...201121976650
date palm sap linked to nipah virus outbreak in bangladesh, 2008.abstract introduction: we investigated a cluster of patients with encephalitis in the manikgonj and rajbari districts of bangladesh in february 2008 to determine the etiology and risk factors for disease. methods: we classified persons as confirmed nipah cases by the presence of immunoglobulin m antibodies against nipah virus (niv), or by the presence of niv rna or by isolation of niv from cerebrospinal fluid or throat swabs who had onset of symptoms between february 6 and march 10, 2008. we ...201121923274
display of the antigenic region of nipah virus nucleocapsid protein on hepatitis b virus capsid.the c-terminal domain of nipah virus (niv) nucleocapsid protein (np(401-532)) was inserted at the n-terminus and the immunodominant loop of hepatitis b core antigen (hbc). the stability of np(401-532) increased tremendously when displayed on the hbc particles. these particles reacted specifically with the swine anti-niv and the human anti-hbc antisera.201122024533
mri findings in acute hendra virus meningoencephalitis.aim: to describe serial changes in brain magnetic resonance imaging (mri) in acute human infection from two outbreaks of hendra virus (hev), relate these changes to disease prognosis, and compare hev encephalitis to reported cases of nipah virus encephalitis. materials and methods: the mri images of three human cases (two of which were fatal) of acute hev meningoencephalitis were reviewed. results: cortical selectivity early in the disease is evident in all three patients, while deep white matte ...201122133593
nipah virus. 201121984987
nipah virus transmission in a hamster model.based on epidemiological data, it is believed that human-to-human transmission plays an important role in nipah virus outbreaks. no experimental data are currently available on the potential routes of human-to-human transmission of nipah virus. in a first dose-finding experiment in syrian hamsters, it was shown that nipah virus was predominantly shed via the respiratory tract within nasal and oropharyngeal secretions. although nipah viral rna was detected in urogenital and rectal swabs, no infec ...201122180802
ephrin-b2 and ephrin-b3 as functional henipavirus receptors.members of the ephrin cell-surface protein family interact with the eph receptors, the largest family of receptor tyrosine kinases, mediating bi-directional signaling during tumorogenesis and various developmental events. surprisingly, ephrin-b2 and -b3 were recently identified as entry receptors for henipaviruses, emerging zoonotic paramyxoviruses responsible for repeated outbreaks in humans and animals in australia, southeast asia, india and bangladesh. nipah virus (niv) and hendra virus (hev) ...201122227101
henipaviruses-unanswered questions of lethal zoonoses.the highly lethal hendra and nipah viruses have been described for little more than a decade, yet within that time have been aetiologically associated with major livestock and human health impacts, albeit on a limited scale. do these emerging pathogens pose a broader threat, or are they inconsequential 'viral chatter'. given their lethality, and the evident multi-generational human-to-human transmission associated with nipah virus in bangladesh, it seems prudent to apply the precautionary princi ...201122440924
characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: implications for mechanisms of immune evasion and design of vaccine immunogens.we have previously observed that all known hiv-1 broadly neutralizing antibodies (bnabs) are highly divergent from germline antibodies in contrast to bnabs against hendra virus, nipah virus and sars coronavirus (sars cov). we have hypothesized that because the germline antibodies are so different from the mature hiv-1-specific bnabs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predece ...201122226962
good governance in 'one health' approaches.the authors discuss 'one health' approaches for controlling newly recognised and re-emerging diseases of animal origin and contributions towards pandemic preparedness based on enhanced collaboration between veterinary services, human health services and environmental services. improved veterinary governance and cooperation with public health managers, social scientists, ecologists and many other stakeholders are important for reducing the risks of potential zoonoses--including foodborne diseases ...201223413734
genetic ancestor of external antigens of pandemic influenza a/h1n1 virus.the aim of the present investigation was to discover the genetic relationships of 2009 pandemic novel influenza a/h1n1 virus (niv) external antigens hemagglutinin (ha) and neuraminidase (na) with other influenza viruses by performing phylogenetic, comparative and statistical analyses. phylogenetic trees of these two antigens show that the sequences of the niv viruses are relatively homogeneous and these were derived from several viruses circulating in swine. the phylogenetic tree of ha shows tha ...201223354817
bats and their virome: an important source of emerging viruses capable of infecting humans.bats are being increasingly recognized as an important reservoir of zoonotic viruses of different families, including sars coronavirus, nipah virus, hendra virus and ebola virus. several recent studies hypothesized that bats, an ancient group of flying mammals, are the major reservoir of several important rna virus families from which other mammalian viruses of livestock and humans were derived. although this hypothesis needs further investigation, the premise that bats carry a large number of v ...201223265969
interdisciplinary approaches to understanding disease emergence: the past, present, and future drivers of nipah virus emergence.emerging infectious diseases (eids) pose a significant threat to human health, economic stability, and biodiversity. despite this, the mechanisms underlying disease emergence are still not fully understood, and control measures rely heavily on mitigating the impact of eids after they have emerged. here, we highlight the emergence of a zoonotic henipavirus, nipah virus, to demonstrate the interdisciplinary and macroecological approaches necessary to understand eid emergence. previous work suggest ...201222936052
independent structural domains in the paramyxovirus polymerase protein.all enzymatic activities required for genomic replication and transcription of nonsegmented negative strand rna viruses (nnsv or mononegavirales) are believed to be concentrated in the viral polymerase (l) protein. however, our insight into the organization of these different enzymatic activities into a bioactive tertiary structure remains rudimentary. fragments of mononegavirales polymerases analyzed to date cannot restore bioactivity through trans-complementation, unlike the related l proteins ...201222215662
emerging and re-emerging swine viruses.in the past two decades or so, a number of viruses have emerged in the global swine population. some, such as porcine reproductive and respiratory syndrome virus (prrsv) and porcine circovirus type 2 (pcv2), cause economically important diseases in pigs, whereas others such as porcine torque teno virus (ttv), now known as torque teno sus virus (ttsuv), porcine bocavirus (pbov) and related novel parvoviruses, porcine kobuvirus, porcine toroviruses (ptov) and porcine lymphotropic herpesviruses (pl ...201222225855
n-glycans on the nipah virus attachment glycoprotein modulate fusion and viral entry as they protect against antibody neutralization.nipah virus (niv) is the deadliest known paramyxovirus. membrane fusion is essential for niv entry into host cells and for the virus' pathological induction of cell-cell fusion (syncytia). the mechanism by which the attachment glycoprotein (g), upon binding to the cell receptors ephrinb2 or ephrinb3, triggers the fusion glycoprotein (f) to execute membrane fusion is largely unknown. n-glycans on paramyxovirus glycoproteins are generally required for proper protein conformational integrity, trans ...201222915812
molecular diagnostic and genetic characterization of highly pathogenic viruses: application during crimean-congo haemorrhagic fever virus outbreaks in eastern europe and the middle east.several haemorrhagic fevers are caused by highly pathogenic viruses that must be handled in biosafety level 4 (bsl-4) containment. these zoonotic infections have an important impact on public health and the development of a rapid and differential diagnosis in case of outbreak in risk areas represents a critical priority. we have demonstrated the potential of a dna resequencing microarray (pathogenid v2.0) for this purpose. the microarray was first validated in vitro using supernatants of cells i ...201223240764
second generation of pseudotype-based serum neutralization assay for nipah virus antibodies: sensitive and high-throughput analysis utilizing secreted alkaline phosphatase.nipah virus (niv), paramyxoviridae, henipavirus, is classified as a biosafety level (bsl) 4 pathogen, along with the closely related hendra virus (hev). a novel serum neutralization test was developed for measuring niv neutralizing antibodies under bsl2 conditions using a recombinant vesicular stomatitis virus (vsv) expressing secreted alkaline phosphatase (seap) and pseudotyped with niv f/g proteins (vsv-niv-seap). a unique characteristic of this novel assay is the ability to obtain neutralizat ...201222115786
bats host major mammalian paramyxoviruses.the large virus family paramyxoviridae includes some of the most significant human and livestock viruses, such as measles-, distemper-, mumps-, parainfluenza-, newcastle disease-, respiratory syncytial virus and metapneumoviruses. here we identify an estimated 66 new paramyxoviruses in a worldwide sample of 119 bat and rodent species (9,278 individuals). major discoveries include evidence of an origin of hendra- and nipah virus in africa, identification of a bat virus conspecific with the human ...201222531181
new insights into the hendra virus attachment and entry process from structures of the virus g glycoprotein and its complex with ephrin-b2.hendra virus and nipah virus, comprising the genus henipavirus, are recently emerged, highly pathogenic and often lethal zoonotic agents against which there are no approved therapeutics. two surface glycoproteins, the attachment (g) and fusion (f), mediate host cell entry. the crystal structures of the hendra g glycoprotein alone and in complex with the ephrin-b2 receptor reveal that henipavirus uses tryptophan 122 on ephrin-b2/b3 as a "latch" to facilitate the g-receptor association. structural ...201223144952
biochemical, conformational, and immunogenic analysis of soluble trimeric forms of henipavirus fusion glycoproteins.the henipaviruses, hendra virus (hev) and nipah virus (niv), are paramyxoviruses discovered in the mid- to late 1990s that possess a broad host tropism and are known to cause severe and often fatal disease in both humans and animals. hev and niv infect cells by a ph-independent membrane fusion mechanism facilitated by their attachment (g) and fusion (f) glycoproteins. here, several soluble forms of henipavirus f (sf) were engineered and characterized. recombinant sf was produced by deleting the ...201222915804
cedar virus: a novel henipavirus isolated from australian bats.the genus henipavirus in the family paramyxoviridae contains two viruses, hendra virus (hev) and nipah virus (niv) for which pteropid bats act as the main natural reservoir. each virus also causes serious and commonly lethal infection of people as well as various species of domestic animals, however little is known about the associated mechanisms of pathogenesis. here, we report the isolation and characterization of a new paramyxovirus from pteropid bats, cedar virus (cedpv), which shares signif ...201222879820
a hendra virus g glycoprotein subunit vaccine protects african green monkeys from nipah virus challenge.in the 1990s, hendra virus and nipah virus (niv), two closely related and previously unrecognized paramyxoviruses that cause severe disease and death in humans and a variety of animals, were discovered in australia and malaysia, respectively. outbreaks of disease have occurred nearly every year since niv was first discovered, with case fatality ranging from 10 to 100%. in the african green monkey (agm), niv causes a severe lethal respiratory and/or neurological disease that essentially mirrors f ...201222875827
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
introduction: nipah virus--discovery and origin.until the nipah outbreak in malaysia in 1999, knowledge of human infections with the henipaviruses was limited to the small number of cases associated with the emergence of hendra virus in australia in 1994. the nipah outbreak in malaysia alerted the global public health community to the severe pathogenic potential and widespread distribution of these unique paramyxoviruses. this chapter briefly describes the initial discovery of nipah virus and the challenges encountered during the initial iden ...201222782307
epidemiology of henipavirus disease in humans.all seven recognized human cases of hendra virus (hev) infection have occurred in queensland, australia. recognized human infections have all resulted from a hev infected horse that was unusually efficient in transmitting the virus and a person with a high exposure to infectious secretions. in the large outbreak in malaysia where nipah virus (niv) was first identified, most human infections resulted from close contact with niv infected pigs. outbreak investigations in bangladesh have identified ...201222752412
nonstructural nipah virus c protein regulates both the early host proinflammatory response and viral virulence.nipah virus (niv) is a highly pathogenic, negative-strand rna paramyxovirus that has recently emerged from flying foxes to cause serious human disease. we have analyzed the role of the nonstructural niv c protein in viral immunopathogenesis using recombinant virus lacking the expression of niv c (nivδc). while wild-type niv was highly pathogenic in the hamster animal model, nivδc was strongly attenuated. replication of nivδc was followed by the production of niv-specific antibodies and associate ...201222837207
detection of nipah virus rna in fruit bat (pteropus giganteus) from india.the study deals with the survey of different bat populations (pteropus giganteus, cynopterus sphinx, and megaderma lyra) in india for highly pathogenic nipah virus (niv), reston ebola virus, and marburg virus. bats (n = 140) from two states in india (maharashtra and west bengal) were tested for igg (serum samples) against these viruses and for virus rnas. only niv rna was detected in a liver homogenate of p. giganteus captured in myanaguri, west bengal. partial sequence analysis of nucleocapsid, ...201222802440
the immune response to nipah virus infection.nipah virus has recently emerged as a zoonotic agent that is highly pathogenic in humans. outbreaks have occurred regularly over the last two decades in south and southeast asia, where mortality rates reach as high as 100 %. the natural reservoir of nipah virus has been identified as bats from the pteropus family, where infection is largely asymptomatic. human disease is characterized by both respiratory and encephalitic components, and thus far, no effective vaccine or intervention strategies a ...201222669317
cysteines in the stalk of the nipah virus g glycoprotein are located in a distinct subdomain critical for fusion activation.paramyxoviruses initiate entry through the concerted action of the tetrameric attachment glycoprotein (hn, h, or g) and the trimeric fusion glycoprotein (f). the ectodomains of hn/h/g contain a stalk region important for oligomeric stability and for the f triggering resulting in membrane fusion. paramyxovirus hn, h, and g form a dimer-of-dimers consisting of disulfide-linked dimers through their stalk domain cysteines. the g attachment protein stalk domain of the highly pathogenic nipah virus (n ...201222496210
rapid screening for entry inhibitors of highly pathogenic viruses under low-level biocontainment.emerging viruses including nipah, hendra, lujo, and junin viruses have enormous potential to spread rapidly. nipah virus, after emerging as a zoonosis, has also evolved the capacity for human-to-human transmission. most of the diseases caused by these pathogens are untreatable and require high biocontainment conditions. universal methods for rapidly identifying and screening candidate antivirals are urgently needed. we have developed a modular antiviral platform strategy that relies on simple bi ...201222396728
lethal nipah virus infection induces rapid overexpression of cxcl10.nipah virus (niv) is a recently emerged zoonotic paramyxovirus that causes regular outbreaks in east asia with mortality rate exceeding 75%. major cellular targets of niv infection are endothelial cells and neurons. to better understand virus-host interaction, we analyzed the transcriptome profile of niv infection in primary human umbilical vein endothelial cells. we further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from niv-inf ...201222393386
serologic evidence of nipah virus infection in bats, vietnam. 201222377109
characterization of nipah virus from outbreaks in bangladesh, 2008-2010.nipah virus (niv) is a highly pathogenic paramyxovirus that causes fatal encephalitis in humans. the initial outbreak of niv infection occurred in malaysia and singapore in 1998-1999; relatively small, sporadic outbreaks among humans have occurred in bangladesh since 2001. we characterized the complete genomic sequences of identical niv isolates from 2 patients in 2008 and partial genomic sequences of throat swab samples from 3 patients in 2010, all from bangladesh. all sequences from patients i ...201222304936
nipah virus infects specific subsets of porcine peripheral blood mononuclear cells.nipah virus (niv), a zoonotic paramyxovirus, is highly contagious in swine, and can cause fatal infections in humans following transmission from the swine host. the main viral targets in both species are the respiratory and central nervous systems, with viremia implicated as a mode of dissemination of niv throughout the host. the presented work focused on the role of peripheral blood mononuclear cells (pbmc) in the viremic spread of the virus in the swine host. b lymphocytes, cd4-cd8-, as well a ...201222303463
activation of the nipah virus fusion protein in mdck cells is mediated by cathepsin b within the endosome-recycling compartment.proteolytic activation of the fusion protein of the highly pathogenic nipah virus (niv f) is a prerequisite for the production of infectious particles and for virus spread via cell-to-cell fusion. unlike other paramyxoviral fusion proteins, functional niv f activation requires endocytosis and ph-dependent cleavage at a monobasic cleavage site by endosomal proteases. using prototype vero cells, cathepsin l was previously identified to be a cleavage enzyme. compared to vero cells, mdck cells showe ...201222278224
transmission routes for nipah virus from malaysia and bangladesh.human infections with nipah virus in malaysia and bangladesh are associated with markedly different patterns of transmission and pathogenicity. to compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the malaysia or bangladesh strain of nipah virus. viral shedding and tissue tropism were compared between the 2 groups. over the course of infection, significantly higher levels of viral rna were recovered from oral secretions of ferrets ...201223171621
re-emergence nipah - a review.there was an outbreak of new emergence viral encephalitis caused by nipah virus among humans in some areas of bangladesh during 2001 - till to date. the disease affected mainly the young, had increased suspicion to spread from bat to man through eating of the same fruits. the risk of human-to-human transmission is thought to be low though many of the affected individuals belonged to the same family. the disease presented mainly as acute encephalitis with usually a short incubation period of less ...201223134935
distinct and overlapping roles of nipah virus p gene products in modulating the human endothelial cell antiviral response.nipah virus (niv) is a highly pathogenic zoonotic paramyxovirus that causes fatal encephalitis in up to 75% of infected humans. like other paramyxoviruses, niv employs co-transcriptional mrna editing during transcription of the phosphoprotein (p) gene to generate additional mrnas encoding the v and w proteins. the c protein is translated from the p mrna, but in an alternative reading frame. there is evidence from both in vitro and in vivo studies to show that the p gene products play a role in n ...201223094089
rapid nipah virus entry into the central nervous system of hamsters via the olfactory route.encephalitis is a hallmark of nipah virus (niv) infection in humans. the exact route of entry of niv into the central nervous system (cns) is unknown. here, we performed a spatio-temporal analysis of niv entry into the cns of hamsters. niv initially predominantly targeted the olfactory epithelium in the nasal turbinates. from there, niv infected neurons were visible extending through the cribriform plate into the olfactory bulb, providing direct evidence of rapid cns entry. subsequently, niv dis ...201223071900
a randomized controlled trial of interventions to impede date palm sap contamination by bats to prevent nipah virus transmission in bangladesh.drinking raw date palm sap is a risk factor for human nipah virus (niv) infection. fruit bats, the natural reservoir of niv, commonly contaminate raw sap with saliva by licking date palm's sap producing surface. we evaluated four types of physical barriers that may prevent bats from contacting sap.201222905160
antigen capture elisa system for henipaviruses using polyclonal antibodies obtained by dna immunization.a novel antigen-capture sandwich elisa system targeting the glycoproteins of the henipaviruses nipah virus (niv) and hendra virus (hev) was developed. utilizing purified polyclonal antibodies derived from niv glycoprotein-encoding dna-immunized rabbits, we established a system that can detect the native antigenic structures of the henipavirus surface glycoproteins using simplified and inexpensive methods. the lowest detection limit against live viruses was achieved for niv bangladesh strain, 2.5 ...201222585045
nipah and hendra virus interactions with the innate immune system.nipah virus and hendra virus are related, highly pathogenic paramyxoviruses with unusually broad host ranges. henipaviruses encode several proteins that block innate immune responses, and these are likely to serve as virulence factors. specfically, four virus-encoded proteins, the phosphoprotein (p), the v protein, the w protein, and the c protein have each been demonstrated to counteract aspects of the interferon (ifn)-α/β response, a key component of the innate immune response to virus infecti ...201222491899
henipavirus outbreaks to antivirals: the current status of potential therapeutics.the henipaviruses, hendra virus and nipah virus, are classic examples of recently emerged viral zoonoses. in a relatively short time since their discoveries in the mid and late 1990s, respectively, a great deal of new information has been accumulated detailing their biology and certain unique characteristics. their broad species tropism and abilities to cause severe and often fatal respiratory and/or neurologic disease in both animals and humans has sparked considerable interest in developing ef ...201222482714
immunization strategies against henipaviruses.hendra virus and nipah virus are recently discovered and closely related emerging viruses that now comprise the genus henipavirus within the sub-family paramyxoviridae and are distinguished by their broad species tropism and in addition to bats can infect and cause fatal disease in a wide variety of mammalian hosts including humans. the high mortality associated with human and animal henipavirus infections has highlighted the importance and necessity of developing effective immunization strategi ...201222481140
animal challenge models of henipavirus infection and pathogenesis.the henipaviruses, hendra virus (hev), and nipah virus (niv), are enigmatic emerging pathogens that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. amongst people, case fatality rates range between 40 and 75% and there are no vaccines or treatments approved for human use. a number of species of animals including guinea pigs, hamsters, cats, ferrets, pigs, and african green monkeys have been employed as animal models of human henipavirus infection. ...201222476556
henipaviruses in their natural animal hosts.hendra virus (hev) and nipah virus (niv) form a separate genus henipavirus within the family paramyxoviridae, and are classified as biosafety level 4 pathogens due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy. both viruses emerged from their natural reservoir during the last decade of the twentieth century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. the current revie ...201222476529
clinical and pathological manifestations of human henipavirus infection.the clinicopathological features of human nipah virus and hendra virus infections appear to be similar. the clinical manifestations may be mild, but if severe, includes acute encephalitic and pulmonary syndromes with a high mortality. the pathological features in human acute henipavirus infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis), microinfarcts and parenchymal cell infection in the central nervous system, lung, kidney and other major organs. vir ...201222427144
qualitative release assessment to estimate the likelihood of henipavirus entering the united kingdom.the genus henipavirus includes hendra virus (hev) and nipah virus (niv), for which fruit bats (particularly those of the genus pteropus) are considered to be the wildlife reservoir. the recognition of henipaviruses occurring across a wider geographic and host range suggests the possibility of the virus entering the united kingdom (uk). to estimate the likelihood of henipaviruses entering the uk, a qualitative release assessment was undertaken. to facilitate the release assessment, the world was ...201222328916
a general strategy to endow natural fusion-protein-derived peptides with potent antiviral activity.fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy.viral fusion is driven by specialized proteins which, although specific to each virus, act through a common mechanism, the formation of a complex between two heptad repeat (hr) regions. the hr regions are initially separated in an intermediate termed "prehairpin", which bridges the viral and cell membranes, a ...201222666328
the second receptor binding site of the globular head of the newcastle disease virus hemagglutinin-neuraminidase activates the stalk of multiple paramyxovirus receptor binding proteins to trigger fusion.the hemagglutinin-neuraminidase (hn) protein of paramyxoviruses carries out three distinct activities contributing to the ability of hn to promote viral fusion and entry: receptor binding, receptor cleavage (neuraminidase), and activation of the fusion protein. the relationship between receptor binding and fusion triggering functions of hn are not fully understood. for newcastle disease virus (ndv), one bifunctional site (site i) on hn's globular head can mediate both receptor binding and neuram ...201222438532
inhibition of virus-like particle release of sendai virus and nipah virus, but not that of mumps virus, by tetherin/cd317/bst-2.tetherin (also known as bst-2 or cd317) has recently been identified as a potent ifn-induced anti-viral protein that inhibits the release of diverse enveloped virus particles from infected cells. the anti-viral activity of tetherin on a number of enveloped viruses, including retroviruses, filoviruses and arenaviruses, has been examined. here, we show that tetherin is also capable of blocking the release of virus-like particles (vlps) driven by the matrix protein of sendai virus. together with in ...201223077864
inhibition of interferon regulatory factor 3 activation by paramyxovirus v protein.the v protein of sendai virus (sev) suppresses innate immunity, resulting in enhancement of viral growth in mouse lungs and viral pathogenicity. the innate immunity restricted by the v protein is induced through activation of interferon regulatory factor 3 (irf3). the v protein has been shown to interact with melanoma differentiation-associated gene 5 (mda5) and to inhibit beta interferon production. in the present study, we infected mda5-knockout mice with v-deficient sev and found that mda5 wa ...201222532687
newcastle disease virus-vectored nipah encephalitis vaccines induce b and t cell responses in mice and long-lasting neutralizing antibodies in pigs.nipah virus (niv), a member of the paramyxoviridae family, causes deadly encephalitis in humans and huge economic losses to the pig industry. here, we generated recombinant avirulent newcastle disease virus (ndv) lasota strains expressing the niv g and f proteins respectively (designated as rla-nivg and rla-nivf), and evaluated their immunogenicity in mice and pigs. both rla-nivg and rla-nivf displayed growth properties similar to those of lasota virus in chicken eggs. co-infection of rla-nivg a ...201222726244
identification of a region in the stalk domain of the nipah virus receptor binding protein that is critical for fusion activation.paramyxoviruses, including the emerging lethal human nipah virus (niv) and the avian newcastle disease virus (ndv), enter host cells through fusion of the viral and target cell membranes. for paramyxoviruses, membrane fusion is the result of the concerted action of two viral envelope glycoproteins: a receptor binding protein and a fusion protein (f). the niv receptor binding protein (g) attaches to ephrin b2 or b3 on host cells, whereas the corresponding hemagglutinin-neuraminidase (hn) attachme ...201323903846
individual n-glycans added at intervals along the stalk of the nipah virus g protein prevent fusion but do not block the interaction with the homologous f protein.the promotion of membrane fusion by most paramyxoviruses requires an interaction between the viral attachment and fusion (f) proteins to enable receptor binding by the former to trigger the activation of the latter for fusion. numerous studies demonstrate that the f-interactive sites on the newcastle disease virus (ndv) hemagglutinin-neuraminidase (hn) and measles virus (mv) hemagglutinin (h) proteins reside entirely within the stalk regions of those proteins. indeed, stalk residues of ndv hn an ...201323283956
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
assessing induced folding within the intrinsically disordered c-terminal domain of the henipavirus nucleoproteins by site-directed spin labeling epr spectroscopy.this work aims at characterizing structural transitions within the intrinsically disordered c-terminal domain of the nucleoprotein (ntail) from the nipah and hendra viruses, two recently emerged pathogens gathered within the henipavirus genus. to this end, we used site-directed spin labeling combined with electron paramagnetic resonance spectroscopy to investigate the α-helical-induced folding that henipavirus ntail domains undergo in the presence of the c-terminal x domain of the phosphoprotein ...201322881220
comparison of the pathogenicity of nipah virus isolates from bangladesh and malaysia in the syrian hamster.nipah virus is a zoonotic pathogen that causes severe disease in humans. the mechanisms of pathogenesis are not well described. the first nipah virus outbreak occurred in malaysia, where human disease had a strong neurological component. subsequent outbreaks have occurred in bangladesh and india and transmission and disease processes in these outbreaks appear to be different from those of the malaysian outbreak. until this point, virtually all nipah virus studies in vitro and in vivo, including ...201323342177
detection of receptor-induced glycoprotein conformational changes on enveloped virions by using confocal micro-raman spectroscopy.conformational changes in the glycoproteins of enveloped viruses are critical for membrane fusion, which enables viral entry into cells and the pathological cell-cell fusion (syncytia) associated with some viral infections. however, technological capabilities for identifying viral glycoproteins and their conformational changes on actual enveloped virus surfaces are generally scarce, challenging, and time-consuming. our model, nipah virus (niv), is a syncytium-forming biosafety level 4 pathogen w ...201323283947
nipah virus entry and egress from polarized epithelial cells.highly pathogenic nipah virus (niv) infections are transmitted via airway secretions and urine, commonly via the respiratory route. epithelial surfaces represent important replication sites in both primary and systemic infection phases. niv entry and spread from polarized epithelial cells therefore determine virus entry and dissemination within a new host and influence virus shedding via mucosal surfaces in the respiratory and urinary tract. to date, there is no knowledge regarding the entry and ...201323283941
[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
risk factors for nipah virus infection among pteropid bats, peninsular malaysia.we conducted cross-sectional and longitudinal studies to determine the distribution of and risk factors for seropositivity to nipah virus (niv) among pteropus vampyrus and p. hypomelanus bats in peninsular malaysia. neutralizing antibodies against niv were detected at most locations surveyed. we observed a consistently higher niv risk (odds ratio 3.9) and seroprevalence (32.8%) for p. vampyrus than p. hypomelanus (11.1%) bats. a 3-year longitudinal study of p. hypomelanus bats indicated nonseaso ...201323261015
nipah virus envelope-pseudotyped lentiviruses efficiently target ephrinb2-positive stem cell populations in vitro and bypass the liver sink when administered in vivo.sophisticated retargeting systems for lentiviral vectors have been developed in recent years. most seek to suppress the viral envelope's natural tropism while modifying the receptor-binding domain such that its tropism is determined by the specificity of the engineered ligand-binding motif. here we took advantage of the natural tropism of nipah virus (niv), whose attachment envelope glycoprotein has picomolar affinity for ephrinb2, a molecule proposed as a molecular marker of "stemness" (present ...201323192877
surface glycoproteins of an african henipavirus induce syncytium formation in a cell line derived from an african fruit bat, hypsignathus monstrosus.serological screening and detection of genomic rna indicates that members of the genus henipavirus are present not only in southeast asia but also in african fruit bats. we demonstrate that the surface glycoproteins f and g of an african henipavirus (m74) induce syncytium formation in a kidney cell line derived from an african fruit bat, hypsignathus monstrosus. despite a less broad cell tropism, the m74 glycoproteins show functional similarities to glycoproteins of nipah virus.201324067951
the pandemic potential of nipah virus.nipah virus, a paramyxovirus whose wildlife reservoir is pteropus bats, was first discovered in a large outbreak of acute encephalitis in malaysia in 1998 among persons who had contact with sick pigs. apparently, one or more pigs was infected from bats, and the virus then spread efficiently from pig to pig, then from pigs to people. nipah virus outbreaks have been recognized nearly every year in bangladesh since 2001 and occasionally in neighboring india. outbreaks in bangladesh and india have b ...201323911335
nipah virus in the fruit bat pteropus vampyrus in sumatera, indonesia.nipah virus causes periodic livestock and human disease with high case fatality rate, and consequent major economic, social and psychological impacts. fruit bats of the genus pteropus are the natural reservoir. in this study, we used real time pcr to screen the saliva and urine of p. vampyrus from north sumatera for nipah virus genome. a conventional reverse transcriptase (rt-pcr) assay was used on provisionally positive samples to corroborate findings. this is the first report of nipah virus de ...201323894501
vaccination of ferrets with a recombinant g glycoprotein subunit vaccine provides protection against nipah virus disease for over 12 months.nipah virus (niv) is a zoonotic virus belonging to the henipavirus genus in the family paramyxoviridae. since niv was first identified in 1999, outbreaks have continued to occur in humans in bangladesh and india on an almost annual basis with case fatality rates reported between 40% and 100%.201323867060
[the concept of emerging viral diseases: what risk for reunion island?].in reunion island, the risk of emerging infectious diseases lies mainly in several viral zoonoses: west nile fever, sindbis virus, nipah virus, wesselsbron virus, rift valley fever and japanese encephalitis. there morbidity and consequences are more or less important but they all have a non-negligible epidemic potential, so they have to be monitored. indeed, the struggle against these emerging infectious diseases requires an early detection of the cases, thus a surveillance system capable of det ...201323765703
socio-economic, industrial and cultural parameters of pig-borne infections.the pork-processing industry has been possibly the fastest growing sector of the food industry in recent years. specialization, genetic homogenization of the pig population, high density of the breeding population, reduced human-animal interactions, slaughter at a lower age and increased international trade of live animals and pork are parameters that affect, positively or negatively, the emergence of novel pig-borne pathogens, many of which are pig-specific, and many of which have significant z ...201323738656
characterization of a third generation lentiviral vector pseudotyped with nipah virus envelope proteins for endothelial cell transduction.lentiviruses are becoming progressively more popular as gene therapy vectors due to their ability to integrate into quiescent cells and recent clinical trial successes. directing these vectors to specific cell types and limiting off-target transduction in vivo remains a challenge. replacing the viral envelope proteins responsible for cellular binding, or pseudotyping, remains a common method to improve lentiviral targeting. here, we describe the development of a high titer, third generation lent ...201323698741
activation and cell death in human dendritic cells infected with nipah virus.nipah virus (niv) is a highly pathogenic paramyxovirus that causes pulmonary disease and encephalitis in humans with 40-70% fatality. interactions between niv and the human immune system remain poorly understood. here, we demonstrate the effects of niv infection on dc and t cell function. using an in vitro system, we found that niv infects and replicates at low levels in dcs and induces the expression of tnf-α, il-1α, il-1β, il-8, and ip-10. niv infection activates dcs, and upregulates the expre ...201323587249
recombinant measles virus vaccine expressing the nipah virus glycoprotein protects against lethal nipah virus challenge.nipah virus (niv) is a member of the genus henipavirus, which emerged in malaysia in 1998. in pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. nipah virus has continued to re-emerge in bangladesh and india, and person-to-person transmission appeared in the outbreak. although a number of niv vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. in this study, we ...201323516477
using routine surveillance data to estimate the epidemic potential of emerging zoonoses: application to the emergence of us swine origin influenza a h3n2v virus.prior to emergence in human populations, zoonoses such as sars cause occasional infections in human populations exposed to reservoir species. the risk of widespread epidemics in humans can be assessed by monitoring the reproduction number r (average number of persons infected by a human case). however, until now, estimating r required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. additionally, existing methods do not correct for i ...201323472057
nipah virus infection outbreak with nosocomial and corpse-to-human transmission, bangladesh.active nipah virus encephalitis surveillance identified an encephalitis cluster and sporadic cases in faridpur, bangladesh, in january 2010. we identified 16 case-patients; 14 of these patients died. for 1 case-patient, the only known exposure was hugging a deceased patient with a probable case, while another case-patient's exposure involved preparing the same corpse for burial by removing oral secretions and anogenital excreta with a cloth and bare hands. among 7 persons with confirmed sporadic ...201323347678
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
unraveling a three-step spatiotemporal mechanism of triggering of receptor-induced nipah virus fusion and cell entry.membrane fusion is essential for entry of the biomedically-important paramyxoviruses into their host cells (viral-cell fusion), and for syncytia formation (cell-cell fusion), often induced by paramyxoviral infections [e.g. those of the deadly nipah virus (niv)]. for most paramyxoviruses, membrane fusion requires two viral glycoproteins. upon receptor binding, the attachment glycoprotein (hn/h/g) triggers the fusion glycoprotein (f) to undergo conformational changes that merge viral and/or cell m ...201324278018
piloting the use of indigenous methods to prevent nipah virus infection by interrupting bats' access to date palm sap in bangladesh.people in bangladesh frequently drink fresh date palm sap. fruit bats (pteropus giganteus) also drink raw sap and may contaminate the sap by shedding nipah virus through saliva and urine. in a previous study we identified two indigenous methods to prevent bats accessing the sap, bamboo skirts and lime (calcium carbonate). we conducted a pilot study to assess the acceptability of these two methods among sap harvesters. we used interactive community meetings and group discussions to encourage all ...201322669914
one health approach in the south east asia region: opportunities and challenges.the outbreaks of sars, avian influenza, and nipah virus in asian countries clearly demonstrated that new highly infectious agents periodically emerge at the human-animal interface. the experiences of regional countries with prevention and control of avian influenza, sars have reinforced the need for sustained, well-coordinated, multi-sector, multi-disciplinary, community-based actions to address emerging disease threats. 'one health' is a cost-effective, sustainable, and practical approach to fi ...201322820705
henipaviruses: an updated review focusing on the pteropid reservoir and features of transmission.the henipaviruses, hendra virus and nipah virus, are pathogens that have emerged from flying foxes in australia and south-east asia to infect both livestock and humans, often fatally. since the emergence of hendra virus in australia in 1994 and the identification of australian flying foxes as hosts to this virus, our appreciation of bats as reservoir hosts of henipaviruses has expanded globally to include much of asia and areas of africa. despite this, little is currently known of the mechanisms ...201322709528
type i interferon signaling protects mice from lethal henipavirus infection.hendra virus (hev) and nipah virus (niv) are closely related, recently emerged paramyxoviruses that form henipavirus genus and are capable of causing considerable morbidity and mortality in a number of mammalian species, including humans. however, in contrast to many other species and despite expression of functional virus entry receptors, mice are resistant to henipavirus infection. we report here the susceptibility of mice deleted for the type i interferon receptor (ifnar-ko) to both hev and n ...201323089589
biochemical and structural studies of the oligomerization domain of the nipah virus phosphoprotein: evidence for an elongated coiled-coil homotrimer.nipah virus (niv) is a recently emerged severe human pathogen that belongs to the henipavirus genus within the paramyxoviridae family. the niv genome is encapsidated by the nucleoprotein (n) within a helical nucleocapsid that is the substrate used by the polymerase for transcription and replication. the polymerase is recruited onto the nucleocapsid via its cofactor, the phosphoprotein (p). the niv p protein has a modular organization, with alternating disordered and ordered domains. among these ...201324074578
the changing face of the henipaviruses.the henipavirus genus represents a group of paramyxoviruses that are some of the deadliest of known human and veterinary pathogens. hendra and nipah viruses are zoonotic pathogens that can cause respiratory and encephalitic illness in humans with mortality rates that exceed 70%. over the past several years, we have seen an increase in the number of cases and an altered clinical presentation of hendra virus in naturally infected horses. recent increase in the number of cases has also been reporte ...201323993256
hendra and nipah infection: emerging paramyxoviruses.since their first emergence in mid 1990s henipaviruses continued to re emerge in australia and south east asia almost every year. in total there has been more than 12 nipah and 48 hendra virus outbreaks reported in south east asia and australia, respectively. these outbreaks are associated with significant economic and health damages that most high risks countries (particularly in south east asia) cannot bear the burden of such economical threats. up until recently, there were no actual therapeu ...201323954578
a treatment for and vaccine against the deadly hendra and nipah viruses.hendra virus and nipah virus are bat-borne paramyxoviruses that are the prototypic members of the genus henipavirus. the henipaviruses emerged in the 1990s, spilling over from their natural bat hosts and causing serious disease outbreaks in humans and livestock. hendra virus emerged in australia and since 1994 there have been 7 human infections with 4 case fatalities. nipah virus first appeared in malaysia and subsequent outbreaks have occurred in bangladesh and india. in total, there have been ...201323838047
use of cross-reactive serological assays for detecting novel pathogens in wildlife: assessing an appropriate cutoff for henipavirus assays in african bats.reservoir hosts of novel pathogens are often identified or suspected as such on the basis of serological assay results, prior to the isolation of the pathogen itself. serological assays might therefore be used outside of their original, validated scope in order to infer seroprevalences in reservoir host populations, until such time that specific diagnostic assays can be developed. this is particularly the case in wildlife disease research. the absence of positive and negative control samples and ...201323835034
current status of diagnostic methods for henipavirus.hendra virus (hev) and nipah virus (niv) are the causative agents of emerging transboundary animal disease in pigs and horses. they also cause fatal disease in humans. niv has a case fatality rate of 40 - 100%. in the initial niv outbreak in malaysia in 1999, about 1.1 million pigs had to be culled. the economic impact was estimated to be approximately us$450 million. worldwide, hev has caused more than 60 deaths in horses with 7 human cases and 4 deaths. since the initial outbreak, hev spillove ...201323689891
passive immunization and active vaccination against hendra and nipah viruses.hendra virus and nipah virus are viral zoonoses first recognized in the mid and late 1990's and are now categorized as the type species of the genus henipavirus within the family paramyxoviridae. their broad species tropism together with their capacity to cause severe and often fatal disease in both humans and animals make hendra and nipah "overlap agents" and significant biosecurity threats. the development of effective vaccination strategies to prevent or treat henipavirus infection and diseas ...201323689890
the distribution of henipaviruses in southeast asia and australasia: is wallace's line a barrier to nipah virus?nipah virus (niv) (genus henipavirus) is a recently emerged zoonotic virus that causes severe disease in humans and has been found in bats of the genus pteropus. whilst niv has not been detected in australia, evidence for niv-infection has been found in pteropid bats in some of australia's closest neighbours. the aim of this study was to determine the occurrence of henipaviruses in fruit bat (family pteropodidae) populations to the north of australia. in particular we tested the hypothesis that ...201323637812
pathogenesis of hendra and nipah virus infection in humans.hendra virus (hev) and nipah virus (niv) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. henipaviruses can infect a wide range of species and human-to-human transmission has been observed for niv. while the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. the limited data on histopathological chang ...201323592639
henipavirus pathogenesis in human respiratory epithelial cells.hendra virus (hev) and nipah virus (niv) are deadly zoonotic viruses for which no vaccines or therapeutics are licensed for human use. henipavirus infection causes severe respiratory illness and encephalitis. although the exact route of transmission in human is unknown, epidemiological studies and in vivo studies suggest that the respiratory tract is important for virus replication. however, the target cells in the respiratory tract are unknown, as are the mechanisms by which henipaviruses can c ...201323302882
protection against henipavirus infection by use of recombinant adeno-associated virus-vector vaccines.nipah virus (niv) and hendra virus (hev) are closely related, recently emerged paramyxoviruses that are capable of causing considerable morbidity and mortality in several mammalian species, including humans. henipavirus-specific vaccines are still commercially unavailable, and development of novel antiviral strategies to prevent lethal infections due to henipaviruses is highly desirable. here we describe the development of adeno-associated virus (aav) vaccines expressing the niv g protein. chara ...201323175762
development of taqman-based qpcr method for detection of caprine arthritis-encephalitis virus (caev) infection.a specific and sensitive two-step taqman real-time pcr has been developed for rapid diagnosis of caprine arthritis-encephalitis virus (caev) infection by using a set of specific primers and a taqman probe targeting a highly conserved region within the gene encoding the viral capsid protein (ca). the assay successfully detected caev proviral dna in total dna extracts originating from cell culture, whole blood samples and isolated pbmcs, with a lower detection limit of 10(2) copies and a linear dy ...201323670072
medical aspects of bio-terrorism.bioterrorism is a terrorist action involving the intentional release or dissemination of a biological warfare agent (bwa), which includes some bacteria, viruses, rickettsiae, fungi or biological toxins. bwa is a naturally occurring or human-modified form that may kill or incapacitate humans, animals or plants as an act of war or terrorism. bwa is a weapon of choice for mass destruction and terrorism, because of the incubation period, less effective amount than chemical warfare agents, easily dis ...201323339855
human monoclonal antibodies as candidate therapeutics against emerging viruses and hiv-1.more than 40 monoclonal antibodies (mabs) have been approved for a number of disease indications with only one of these (synagis) - for a viral disease, and not for therapy but for prevention. however, in the last decade novel potent mabs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including hendra virus (hev), nipah virus (niv), severe acute respiratory syndrome coronavirus (sars-cov), ebola virus (e ...201323575729
transmission potential of influenza a/h7n9, february to may 2013, china.on 31 march 2013, the first human infections with the novel influenza a/h7n9 virus were reported in eastern china. the outbreak expanded rapidly in geographic scope and size, with a total of 132 laboratory-confirmed cases reported by 3 june 2013, in 10 chinese provinces and taiwan. the incidence of a/h7n9 cases has stalled in recent weeks, presumably as a consequence of live bird market closures in the most heavily affected areas. here we compare the transmission potential of influenza a/h7n9 wi ...201324083506
downregulation of nipah virus n mrna occurs through interaction between its 3' untranslated region and hnrnp d.nipah virus (niv) is a nonsegmented, single-stranded, negative-sense rna virus belonging to the genus henipavirus, family paramyxoviridae. niv causes acute encephalitis and respiratory disease in humans, is associated with high mortality, and poses a threat in southern asia. the genomes of henipaviruses are about 18,246 nucleotides (nt) long, which is longer than those of other paramyxoviruses (around 15,384 nt). this difference is caused by the noncoding rna region, particularly the 3' untransl ...201323514888
using network theory to identify the causes of disease outbreaks of unknown origin.the identification of undiagnosed disease outbreaks is critical for mobilizing efforts to prevent widespread transmission of novel virulent pathogens. recent developments in online surveillance systems allow for the rapid communication of the earliest reports of emerging infectious diseases and tracking of their spread. the efficacy of these programs, however, is inhibited by the anecdotal nature of informal reporting and uncertainty of pathogen identity in the early stages of emergence. we deve ...201323389893
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