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recurrent zoonotic transmission of nipah virus into humans, bangladesh, 2001-2007.human nipah outbreaks recur in a specific region and time of year in bangladesh. fruit bats are the reservoir host for nipah virus. we identified 23 introductions of nipah virus into human populations in central and northwestern bangladesh from 2001 through 2007. ten introductions affected multiple persons (median 10). illness onset occurred from december through may but not every year. we identified 122 cases of human nipah infection. the mean age of case-patients was 27 years; 87 (71%) died. i ...200919751584
chloroquine administration does not prevent nipah virus infection and disease in ferrets.hendra virus and nipah virus, two zoonotic paramyxoviruses in the genus henipavirus, have recently emerged and continue to cause sporadic disease outbreaks in humans and animals. mortality rates of up to 75% have been reported in humans, but there are presently no clinically licensed therapeutics for treating henipavirus-induced disease. a recent report indicated that chloroquine, used in malaria therapy for over 70 years, prevented infection with nipah virus in vitro. chloroquine was assessed u ...200919759137
nipah virus entry can occur by macropinocytosis.nipah virus (niv) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in asia with high mortality in man. niv is a member, with hendra virus (hev), of the henipavirus genus in the paramyxoviridae family. although niv entry, like that of other paramyxoviruses, is believed to occur via ph-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. the niv receptor ephrinb2 has receptor kinase activity and we find that ep ...200919854459
transmission of human infection with nipah virus.nipah virus (niv) is a paramyxovirus whose reservoir host is fruit bats of the genus pteropus. occasionally the virus is introduced into human populations and causes severe illness characterized by encephalitis or respiratory disease. the first outbreak of niv was recognized in malaysia, but 8 outbreaks have been reported from bangladesh since 2001. the primary pathways of transmission from bats to people in bangladesh are through contamination of raw date palm sap by bats with subsequent consum ...200919886791
a neutralizing human monoclonal antibody protects against lethal disease in a new ferret model of acute nipah virus infection.nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus henipavirus whose natural reservoirs are several species of pteropus fruit bats. nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. here, a new ferret model of nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. severe disease occurs with viral doses as low ...200919888339
antiviral activity of gliotoxin, gentian violet and brilliant green against nipah and hendra virus in vitro.using a recently described monolayer assay amenable to high throughput screening format for the identification of potential nipah virus and hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds) directly against live virus infection and identified twenty eight promising lead molecules. initial single blind screens were conducted with 10 microm compound in triplicate with a minimum efficacy of 90% required for lead selection. lead compounds ...200919889218
a shared interface mediates paramyxovirus interference with antiviral rna helicases mda5 and lgp2.diverse members of the paramyxovirus family of negative-strand rna viruses effectively suppress host innate immune responses through the actions of their v proteins. the v protein mediates interference with the interferon regulatory rna helicase mda5 to avoid cellular antiviral responses. analysis of the interaction interface revealed the mda5 helicase c domain as necessary and sufficient for association with v proteins from human parainfluenza virus type 2, parainfluenza virus type 5, measles v ...200919403670
characteristics of nipah virus and hendra virus replication in different cell lines and their suitability for antiviral screening.we have recently described the development and validation of a high throughput screening assay suitable for henipavirus antiviral identification. while we are confident this assay is robust and effective, we wished to investigate assay performance in a range of alternative cell lines to determine if assay sensitivity and specificity could be improved. we evaluated ten different cell lines for their susceptibility to hendra and nipah virus infection and their sensitivity of detection of the effec ...200919428741
a neutralization test for specific detection of nipah virus antibodies using pseudotyped vesicular stomatitis virus expressing green fluorescent protein.nipah virus (niv) is a new zoonotic paramyxovirus that emerged in 1998 and is now classified in the genus henipavirus along with the closely related hendra virus (hev). niv is highly pathogenic in several vertebrate species including humans, and the lack of available vaccines or specific treatment restricts it to biosafety level 4 (bsl4) containment. a serum neutralization test was developed for measuring niv neutralizing antibodies under bsl2 conditions using a recombinant vesicular stomatitis ...200919433112
human hendra virus infection causes acute and relapsing encephalitis.to study the pathology of two cases of human hendra virus infection, one with no clinical encephalitis and one with relapsing encephalitis.200919473296
bats and emerging zoonoses: henipaviruses and sars.nearly 75% of all emerging infectious diseases (eids) that impact or threaten human health are zoonotic. the majority have spilled from wildlife reservoirs, either directly to humans or via domestic animals. the emergence of many can be attributed to predisposing factors such as global travel, trade, agricultural expansion, deforestation/habitat fragmentation, and urbanization; such factors increase the interface and/or the rate of contact between human, domestic animal, and wildlife populations ...200919497090
a small-molecule inhibitor of nipah virus envelope protein-mediated membrane fusion.nipah virus (niv), a highly pathogenic paramyxovirus, causes respiratory disease in pigs and severe febrile encephalitis in humans with high mortality rates. on the basis of the structural similarity of viral fusion (f) proteins within the family paramyxoviridae, we designed and tested 18 quinolone derivatives in a niv and measles virus (mv) envelope protein-based fusion assay beside evaluation of cytotoxicity. we found five compounds successfully inhibiting niv envelope protein-induced cell fus ...200919499921
nipah virus sequesters inactive stat1 in the nucleus via a p gene-encoded mechanism.the nipah virus (niv) phosphoprotein (p) gene encodes the c, p, v, and w proteins. p, v, and w, have in common an amino-terminal domain sufficient to bind stat1, inhibiting its interferon (ifn)-induced tyrosine phosphorylation. p is also essential for rna-dependent rna polymerase function. c is encoded by an alternate open reading frame (orf) within the common amino-terminal domain. mutations within residues 81 to 113 of p impaired its polymerase cofactor function, as assessed by a minireplicon ...200919515782
nipah virus infection in dogs, malaysia, 1999.the 1999 outbreak of nipah virus encephalitis in humans and pigs in peninsular malaysia ended with the evacuation of humans and culling of pigs in the epidemic area. serologic screening showed that, in the absence of infected pigs, dogs were not a secondary reservoir for nipah virus.200919523300
generation of tioman virus nucleocapsid-like particles in yeast saccharomyces cerevisiae.tioman virus (tiov) was isolated from a number of pooled urine samples of tioman island flying foxes (pteropus hypomelanus) during the search for the reservoir host of nipah virus. studies have established tiov as a new virus in the family paramyxoviridae. this novel paramyxovirus is antigenically related to menangle virus that was isolated in australia in 1997 during disease outbreak in pigs. tiov causes mild disease in pigs and has a predilection for lymphoid tissues. recent serosurvey showed ...200919559738
development of a neutralization assay for nipah virus using pseudotype particles.nipah virus (niv) and hendra virus (hev) are zoonotic paramyxoviruses capable of causing severe disease in humans and animals. these viruses require biosafety level 4 (bsl-4) containment. like other paramyxoviruses, the plaque reduction neutralization test (prnt) can be used to detect antibodies to the surface glycoproteins, fusion (f) and attachment (g), and prnt titers give an indication of protective immunity. unfortunately, for niv and hev, the prnt must be performed in bsl-4 containment and ...200919559943
henipavirus rna in african bats.henipaviruses (hendra and nipah virus) are highly pathogenic members of the family paramyxoviridae. fruit-eating bats of the pteropus genus have been suggested as their natural reservoir. human henipavirus infections have been reported in a region extending from australia via malaysia into bangladesh, compatible with the geographic range of pteropus. these bats do not occur in continental africa, but a whole range of other fruit bats is encountered. one of the most abundant is eidolon helvum, th ...200919636378
henipaviruses employ a multifaceted approach to evade the antiviral interferon response.hendra and nipah virus, which constitute the genus henipavirus, are zoonotic paramyxoviruses that have been associated with sporadic outbreaks of severe disease and mortality in humans since their emergence in the late 1990s. similar to other paramyxoviruses, their ability to evade the host interferon (ifn) response is conferred by the p gene. the henipavirus p gene encodes four proteins; the p, v, w and c proteins, which have all been described to inhibit the antiviral response. further studies ...200921994589
callosal holes: an unusual imaging appearance in systemic lupus erythematosus. a case report.systemic lupus erythematosus (sle) has diverse imaging features. however, focal lesions in the corpus callosum are extremely rare in sle with only few cases mentioned in the literature, with no mention of callosal holes in sle. callosal holes have been described as a characteristic finding in susac syndrome and have been mentioned in nipah virus encephalitis, marchiafava bignami disease and periventricular leukomalacia. we describe a case of sle with callosal holes. the demonstration of callosal ...200924207034
henipavirus infection in fruit bats (pteropus giganteus), india.we tested 41 bats for antibodies against nipah and hendra viruses to determine whether henipaviruses circulate in pteropid fruit bats (pteropus giganteus) in northern india. twenty bats were seropositive for nipah virus, which suggests circulation in this species, thereby extending the known distribution of henipaviruses in asia westward by >1,000 km.200818680665
inhibition of henipavirus infection by rna interference.nipah virus (niv) and hendra virus (hev) are recently emerged zoonotic paramyxoviruses exclusively grouped within a new genus, henipavirus. these viruses cause fatal disease in a wide range of species, including humans. both niv and hev have continued to re-emerge sporadically in bangladesh and australia, respectively. there are currently no therapeutics or vaccines available to treat henipavirus infection and both are classified as bsl4 pathogens. rna interference (rnai) is a process by which d ...200818687361
ephrin-b2 expression critically influences nipah virus infection independent of its cytoplasmic tail.cell entry and cell-to-cell spread of the highly pathogenic nipah virus (niv) requires binding of the niv g protein to cellular ephrin receptors and subsequent niv f-mediated fusion. since expression levels of the main niv entry receptor ephrin-b2 (eb2) are highly regulated in vivo to fulfill the physiological functions in axon guidance and angiogenesis, the goal of this study was to determine if changes in the eb2 expression influence niv infection.200819108727
selective receptor expression restricts nipah virus infection of endothelial cells.nipah virus (niv) is a highly pathogenic paramyxovirus that causes severe diseases in animals and humans. endothelial cell (ec) infection is an established hallmark of niv infection in vivo. despite systemic virus spread via the vascular system, ec in brain and lung are preferentially infected whereas ec in other organs are less affected. as in vivo, we found differences in the infection of ec in cell culture. only brain-derived primary or immortalized ec were found to be permissive to niv infec ...200819036148
antibodies to nipah or nipah-like viruses in bats, china. 200819046545
a recombinant subunit vaccine formulation protects against lethal nipah virus challenge in cats.nipah virus (niv) and hendra virus (hev) are closely related deadly zoonotic paramyxoviruses that have emerged and re-emerged over the last 10 years. in this study, a subunit vaccine formulation containing only recombinant, soluble, attachment glycoprotein from hev (sg(hev)) and cpg adjuvant was evaluated as a potential niv vaccine in the cat model. different amounts of sg(hev) were employed and sg-induced immunity was examined. vaccinated animals demonstrated varying levels of niv-specific ig s ...200818556094
histopathologic and immunohistochemical characterization of nipah virus infection in the guinea pig.mortality rate in humans infected with nipah virus (niv) has been reported as high as 92%. humans infected with niv show a widespread multisystemic vasculitis with most severe clinical and pathologic manifestations in the brain, lungs, and spleen. the purpose of this study was to study pathologic and immunohistochemical findings in guinea pigs infected with niv. of 28 animals inoculated intraperitoneally, only 2 survived the infection, and most died between 4 and 8 days postinoculation (dpi). vi ...200818587107
host cell recognition by the henipaviruses: crystal structures of the nipah g attachment glycoprotein and its complex with ephrin-b3.nipah virus (niv) and hendra virus are the type species of the highly pathogenic paramyxovirus genus henipavirus, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. niv contains two envelope glycoproteins, the receptor-binding g glycoprotein (niv-g) that facilitates attachment to host cells and the fusion (f) glycoprotein that mediates membrane merger. the henipavirus g glycoproteins lack both hemagglutinating and neu ...200818632560
characterization of the complete genome of influenza a (h5n1) virus isolated during the 2006 outbreak in poultry in india.an outbreak of highly pathogenic avian influenza a (h5n1) virus in poultry was reported from nandurbar and jalgaon districts of maharashtra and adjoining areas of uchhal in gujarat and burhanpur in madhya pradesh in india from january to april, 2006. in the present study, the full genome of two previously uncharacterized strains of h5n1 viruses isolated at the national institute of virology (niv), pune, from post-mortem tissues of chicken collected from navapur, nandurbar district during the out ...200818214665
exceptionally potent cross-reactive neutralization of nipah and hendra viruses by a human monoclonal antibody.we have previously identified neutralizing human monoclonal antibodies against nipah virus (niv) and hendra virus (hev) by panning a large nonimmune antibody library against a soluble form of the hev attachment-envelope glycoprotein g (sg hev). one of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both niv and hev g, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning agains ...200818271743
development and validation of a chemiluminescent immunodetection assay amenable to high throughput screening of antiviral drugs for nipah and hendra virus.there are currently no antiviral drugs approved for the highly lethal biosafety level 4 pathogens nipah and hendra virus. a number of researchers are developing surrogate assays amenable to biosafety level 2 biocontainment but ultimately, the development of a high throughput screening method for directly quantifying these viruses in a biosafety level 4 environment will be critical for final evaluation of antiviral drugs identified in surrogate assays, in addition to reducing the time required fo ...200818313148
[study on the dna immunogenicity of fusion and attachment glycoproteins of nipah virus].the two mammalian codon optimized genes, f and g genes of nipah virus, were generated by assembly pcr, and inserted into mammalian expression vector pcaggs under chicken beta-actin promoter to construct pcagg-niv-f and pcagg-niv-g. syncytium formation was induced in bhk cells by plasmid pcagg-niv-f and pcagg-niv-g transfection, which indicate recombination proteins f and g were expressed in bhk cell and possessed good biologic activity. six-week-old female balb/c mice were intramuscularly primed ...200818320822
role of endocytosis and cathepsin-mediated activation in nipah virus entry.the recent discovery that the nipah virus (niv) fusion protein (f) is activated by endosomal cathepsin l raised the question if niv utilize ph- and protease-dependent mechanisms of entry. we show here that the niv receptor ephrin b2, virus-like particles and infectious niv are internalized from the cell surface. however, endocytosis, acidic ph and cathepsin-mediated cleavage are not necessary for the initiation of infection of new host cells. our data clearly demonstrate that proteolytic activat ...200818342904
identification of a novel coronavirus from a beluga whale by using a panviral microarray.the emergence of viruses such as severe acute respiratory syndrome coronavirus and nipah virus has underscored the role of animal reservoirs in human disease and the need for reservoir surveillance. here, we used a panviral dna microarray to investigate the death of a captive beluga whale in an aquatic park. a highly divergent coronavirus, tentatively named coronavirus sw1, was identified in liver tissue from the deceased whale. subsequently, the entire genome of sw1 was sequenced, yielding a ge ...200818353961
bacterial infections in pigs experimentally infected with nipah virus.nipah virus (niv; paramyxoviridae) caused fatal encephalitis in humans during an outbreak in malaysia in 1998/1999 after transmission from infected pigs. our previous study demonstrated that the respiratory, lymphatic and central nervous systems are targets for virus replication in experimentally infected pigs. to continue the studies on pathogenesis of niv in swine, six piglets were inoculated oronasally with 2.5 x 10(5) pfu per animal. four pigs developed mild clinical signs, one exudative epi ...200818405339
henipavirus v protein association with polo-like kinase reveals functional overlap with stat1 binding and interferon evasion.emerging viruses in the paramyxovirus genus henipavirus evade host antiviral responses via protein interactions between the viral v and w proteins and cellular stat1 and stat2 and the cytosolic rna sensor mda5. polo-like kinase (plk1) is identified as being an additional cellular partner that can bind to nipah virus p, v, and w proteins. for both nipah virus and hendra virus, contact between the v protein and the plk1 polo box domain is required for v protein phosphorylation. results indicate th ...200818417573
the c, v and w proteins of nipah virus inhibit minigenome replication.nipah virus (niv) is a recently emergent, highly pathogenic, zoonotic paramyxovirus of the genus henipavirus. like the phosphoprotein (p) gene of other paramyxoviruses, the p gene of niv is predicted to encode three additional proteins, c, v and w. when the c, v and w proteins of niv were tested for their ability to inhibit expression of the chloramphenicol acetyltransferase (cat) reporter gene in plasmid-based, minigenome replication assays, each protein inhibited cat expression in a dose-depen ...200818420809
induction and sequencing of rousette bat interferon alpha and beta genes.bats are considered to be natural reservoirs for several viruses of clinical importance, including rabies virus, nipah virus, and hendra virus. type i interferons (ifns) is an important part of the immune system in the defense against viral infection. to investigate the function of type i ifns upon viral infection in bats, the nucleic acid, and amino acid sequences of egyptian rousette (rousettus aegyptiacus) ifn-alpha and -beta were characterized. sequence data indicated that bat ifn-alpha cons ...200818436311
clinical presentation of nipah virus infection in bangladesh.in bangladesh, 4 outbreaks of nipah virus infection were identified during the period 2001-2004.200818444812
processing of genome 5' termini as a strategy of negative-strand rna viruses to avoid rig-i-dependent interferon induction.innate immunity is critically dependent on the rapid production of interferon in response to intruding viruses. the intracellular pathogen recognition receptors rig-i and mda5 are essential for interferon induction by viral rnas containing 5' triphosphates or double-stranded structures, respectively. viruses with a negative-stranded rna genome are an important group of pathogens causing emerging and re-emerging diseases. we investigated the ability of genomic rnas from substantial representative ...200818446221
[nipah encephalitis].nipah encephalitis is a particular dangerous disease that affects animals and man. fatal cases of the disease have been identified in the persons looking after pigs in the villages of malaysia. the causative agent is presumably referred to as morbilliviruses of the paramixoviridae family. two hundred persons died among the ill patients with the signs of encephalitis. the principal hosts of the virus were fox-bats (megaschiroptera) inhabiting in the surrounding forests. the present paper descries ...200818450103
structural basis of nipah and hendra virus attachment to their cell-surface receptor ephrin-b2.nipah and hendra viruses are emergent paramyxoviruses, causing disease characterized by rapid onset and high mortality rates, resulting in their classification as biosafety level 4 pathogens. their attachment glycoproteins are essential for the recognition of the cell-surface receptors ephrin-b2 (efnb2) and ephrin-b3 (efnb3). here we report crystal structures of both nipah and hendra attachment glycoproteins in complex with human efnb2. in contrast to previously solved paramyxovirus attachment c ...200818488039
viral encephalitis and epilepsy.viral encephalitis presents with seizures not only in the acute stage but also increases the risk of late unprovoked seizures and epilepsy. acute symptomatic and late unprovoked seizures in different viral encephalitides are reviewed here. among the sporadic viral encephalitides, herpes simplex encephalitis (hse) is perhaps most frequently associated with epilepsy, which may often be severe. seizures may be the presenting feature in 50% patients with hse because of involvement of the highly epil ...200818754956
nipah virus encephalitis.nipah virus was first discovered in 1999, after a severe outbreak of viral encephalitis among pig farm workers in malaysia. the disease is thought to spread from pteropus bats to pigs and then to humans following close contact. the reported mortality rate in this outbreak was 40%. the main necropsy finding in patients with nipah virus encephalitis was disseminated microinfarction associated with vasculitis and direct neuronal involvement. relapse of encephalitis was seen in 10% of those who surv ...200818765105
[emerging viral infections in south east asia and the pacific region].the epidemiology of several viral diseases underwent profound changes in south-east asia and oceania over the past decades. this was due to several factors, including the geographical distribution of vectors and the viruses they transmit; increasing traveling and trade; increasing ecological and demographic pressure. we reviewed the current state of knowledge based on published sources and available epidemiological data. the review was limited to potentially emerging viruses in southeast asia an ...200818771865
crystal structure and carbohydrate analysis of nipah virus attachment glycoprotein: a template for antiviral and vaccine design.two members of the paramyxovirus family, nipah virus (niv) and hendra virus (hev), are recent additions to a growing number of agents of emergent diseases which use bats as a natural host. identification of ephrin-b2 and ephrin-b3 as cellular receptors for these viruses has enabled the development of immunotherapeutic reagents which prevent virus attachment and subsequent fusion. here we present the structural analysis of the protein and carbohydrate components of the unbound viral attachment gl ...200818815311
new respiratory viruses of humans.acute respiratory viruses are a major cause of morbidity and mortality in humans worldwide and most acute respiratory infections are caused by viruses. many of these viruses cause the highest burden of disease in specific risk groups such as young infants, the elderly, and immune-compromised individuals. although the most important respiratory viruses of humans have been identified in the last century, in the past decade about a dozen "new" viruses have been discovered that may cause a high burd ...200818820582
risk factors for nipah virus encephalitis in bangladesh.nipah virus (niv) is a paramyxovirus that causes severe encephalitis in humans. during january 2004, twelve patients with niv encephalitis (nive) were identified in west-central bangladesh. a case-control study was conducted to identify factors associated with niv infection. nive patients from the outbreak were enrolled in a matched case-control study. exact odds ratios (ors) and 95% confidence intervals (cis) were calculated by using a matched analysis. climbing trees (83% of cases vs. 51% of c ...200818826814
the emergence of nipah virus, a highly pathogenic paramyxovirus.nipah virus first emerged in malaysia and singapore between 1998 and 1999, causing severe febrile encephalitis in humans with a mortality rate of close to 40%. in addition, a significant portion of those recovering from acute infection had relapse encephalitis and long-term neurological defects. since its initial outbreak, there have been numerous outbreaks in bangladesh and india, in which the mortality rate rose to approximately 70%. these subsequent outbreaks were distinct from the initial ou ...200818835214
the yplgvg sequence of the nipah virus matrix protein is required for budding.nipah virus (niv) is a recently emerged paramyxovirus capable of causing fatal disease in a broad range of mammalian hosts, including humans. together with hendra virus (hev), they comprise the genus henipavirus in the family paramyxoviridae. recombinant expression systems have played a crucial role in studying the cell biology of these biosafety level-4 restricted viruses. henipavirus assembly and budding occurs at the plasma membrane, although the details of this process remain poorly understo ...200819000317
establishment and characterization of plasmid-driven minigenome rescue systems for nipah virus: rna polymerase i- and t7-catalyzed generation of functional paramyxoviral rna.in this study we report the development and optimization of two minigenome rescue systems for nipah virus, a member of the paramyxoviridae family. one is mediated by the t7 rna polymerase supplied either by a constitutively expressing cell line or by transfection of expression plasmids and is thus independent from infection with a helper virus. the other approach is based on rna polymerase i-driven transcription, a unique approach for paramyxovirus reverse genetics technology. minigenome rescue ...200817904180
monoclonal antibodies against the nucleocapsid proteins of henipaviruses: production, epitope mapping and application in immunohistochemistry.four monoclonal antibodies (mabs) were generated by immunizing balb/c mice with recombinant nucleocapsid protein (n) of nipah virus (niv) and hendra virus (hev) expressed in e. coli. two mabs each were obtained for the hev n and niv n, respectively. all four mabs displayed specific reactivity with the recombinant n proteins of both viruses by western blot, which was further confirmed by immunofluorescent antibody assay using fixed insect cells infected with recombinant baculoviruses expressing e ...200817978885
functional studies of host-specific ephrin-b ligands as henipavirus receptors.hendra virus (hev) and nipah virus (niv) are closely related paramyxoviruses that infect and cause disease in a wide range of mammalian hosts. to determine whether host receptor molecules play a role in species-specific and/or virus-specific infection we have cloned and characterized ephrin-b2 and ephrin-b3 ligands from a range of species, including human, horse, pig, cat, dog, bats (pteropus alecto and pteropus vampyrus) and mouse. hev and niv were both able to infect cells expressing any of th ...200818054977
henipavirus susceptibility to environmental variables.the routes of henipavirus transmission between hosts are poorly understood. the purpose of this study was to measure the persistence of henipaviruses under various environmental conditions and thereby gain an insight into likely mechanisms of transmission. henipaviruses survived for more than 4 days at 22 degrees c in ph-neutral fruit bat urine but were sensitive to higher temperatures and ph changes. on mango flesh, survival time varied depending on temperature and fruit ph, ranging from 2h to ...200818166242
person-to-person transmission of nipah virus in a bangladeshi community.an encephalitis outbreak was investigated in faridpur district, bangladesh, in april-may 2004 to determine the cause of the outbreak and risk factors for disease. biologic specimens were tested for nipah virus. surfaces were evaluated for nipah virus contamination by using reverse transcription-pcr (rt-pcr). thirty-six cases of nipah virus illness were identified; 75% of case-patients died. multiple peaks of illness occurred, and 33 case-patients had close contact with another nipah virus patien ...200718214175
[bad bats?].for many centuries, man is fascinated by bats, the only flying mammals. probably because of their particular immune system, bats can be considered an important reservoir for new emerging viral diseases like sars-coronavirus, marburg fever, ebola fever and nipah virus encephalitis. during closer contact, they can transmit rabies and probably other nonviral infectious diseases. bats get closer to man due to ecological modifications like deforestation, so that transmission of new infectious agents ...200717985603
quantitative analysis of nipah virus proteins released as virus-like particles reveals central role for the matrix protein.nipah virus (niv) is an emerging paramyxovirus distinguished by its ability to cause fatal disease in both animal and human hosts. together with hendra virus (hev), they comprise the genus henipavirus in the paramyxoviridae family. niv and hev are also restricted to biosafety level-4 containment and this has hampered progress towards examining details of their replication and morphogenesis. here, we have established recombinant expression systems to study niv particle assembly and budding throug ...200717204159
inhibition of henipavirus infection by nipah virus attachment glycoprotein occurs without cell-surface downregulation of ephrin-b2 or ephrin-b3.nipah virus (niv) and hendra virus (hev) are newly identified members of the family paramyxoviridae and have been classified in the new genus henipavirus based on unique genetic characteristics distinct from other paramyxoviruses. transgenic cell lines were generated that expressed either the attachment protein (g) or the fusion protein (f) of niv. functional expression of niv f and g was verified by complementation with the corresponding glycoprotein, which resulted in the development of syncyt ...200717251577
emerging viruses: coming in on a wrinkled wing and a prayer.the role that bats have played in the emergence of several new infectious diseases has been under review. bats have been identified as the reservoir hosts of newly emergent viruses such as nipah virus, hendra virus, and severe acute respiratory syndrome-like coronaviruses. this article expands on recent findings about bats and viruses and their relevance to human infections. it briefly reviews the history of chiropteran viruses and discusses their emergence in the context of geography, phylogeny ...200717278066
neutralization assays for differential henipavirus serology using bio-plex protein array systems.hendra virus (hev) and nipah virus (niv) are related emerging paramyxoviruses classified in the genus henipavirus. both cause fatal disease in animals and humans and are classified as biosafety level 4 pathogens. here we detail two new multiplexed microsphere assays, one for antibody detection and differentiation and another designed as a surrogate for virus neutralization. both assays utilize recombinant soluble attachment glycoproteins (sg) whereas the latter incorporates the cellular receptor ...200717292974
polybasic kkr motif in the cytoplasmic tail of nipah virus fusion protein modulates membrane fusion by inside-out signaling.the cytoplasmic tails of the envelope proteins from multiple viruses are known to contain determinants that affect their fusogenic capacities. here we report that specific residues in the cytoplasmic tail of the nipah virus fusion protein (niv-f) modulate its fusogenic activity. truncation of the cytoplasmic tail of niv-f greatly inhibited cell-cell fusion. deletion and alanine scan analysis identified a tribasic kkr motif in the membrane-adjacent region as important for modulating cell-cell fus ...200717301148
expression of truncated phosphoproteins of nipah virus and hendra virus in escherichia coli for the differentiation of henipavirus infections.the genus henipavirus in the family paramyxoviridae compromises two newly identified dangerous pathogens, nipah virus and hendra virus. phosphoprotein of the two viruses is one of the major immunodominant antigens and the most divergent protein in the viral genomes. we have now expressed two pairs of truncated phosphoproteins of the two viruses in escherichia coli in a soluble form using a vector tailored from pet32a. the truncated recombinant phosphoproteins were purified with his-tag affinity ...200717322967
effects of single amino acid substitutions at the e residue in the conserved gdne motif of the nipah virus polymerase (l) protein.nipah virus (niv) is an emergent zoonotic paramyxovirus. the l proteins of most paramyxoviruses contain a gdnq motif, thought to be part of the catalytic site for polymerase activity. conversely, niv l has gdne in this position. we substituted the e residue with eight different amino acid residues and examined the effect on l function in an in vitro replication assay. our results demonstrated that niv l functioned with similar efficiency with either gdne or gdnq, but polymerase activity was seve ...200717143779
duplex nested rt-pcr for detection of nipah virus rna from urine specimens of bats.a method for duplex nested rt-pcr (nrt-pcr) with internal control (ic) for the detection of nipah virus rna is described. incorporation of ic rna distinguished false and true negative results. the extrinsic rna was added directly to the pcr master mix and co-amplified with virus specific rna in a duplex reaction to determine the presence of pcr inhibitor. limit of detection was affected minimally when ic was added. of 53 pooled urine samples collected from fruit bats (pteropus lylei), 16 were va ...200717184850
genetic analysis of j-virus and beilong virus using minireplicons.j-virus (jpv), isolated from wild mice in australia, and beilong virus (beipv), originally isolated from human mesangial cells in china and subsequently detected in rat mesangial cells, represent a new group of paramyxoviruses which have exceptionally large genomes (>19 kb) and contain more than six transcriptional units. in this study, minireplicons were employed to assess the taxonomic status of jpv and beipv. our results demonstrated that, whilst the genome replication machineries of jpv and ...200717397895
proceedings of a meeting entitled emerging viral infectious diseases, april 4-5, 2005, hanoi, vietnam. 200717470907
molecular characteristics of the nipah virus glycoproteins.nipah virus (niv) is a highly pathogenic paramyxovirus, which emerged in 1998 from fruit bats in malaysia and caused an outbreak of severe respiratory disease in pigs and fatal encephalitis in humans with high mortality rates. in contrast to most paramyxoviruses, niv can infect a large variety of mammalian species. due to this broad host range, its zoonotic potential, its high pathogenicity for humans, and the lack of effective vaccines or therapeutics, niv was classified as a biosafety level 4 ...200717470910
envelope-receptor interactions in nipah virus pathobiology.nipah (niv) and hendra (hev) viruses are members of the newly defined henipavirus genus of the paramyxoviridae. nipah virus (niv) is an emergent paramyxovirus that causes fatal encephalitis in up to 70% of infected patients, and there is increasing evidence of human-to-human transmission. niv is designated a priority pathogen in the niaid biodefense research agenda, and could be a devastating agent of agrobioterrorism if used against the pig farming industry. endothelial syncytium is a pathognom ...200717470911
[nipah virus infection]. 200717491382
experimental nipah virus infection in pteropid bats (pteropus poliocephalus).seventeen grey-headed fruit bats (pteropus poliocephalus) were inoculated subcutaneously with an isolate of nipah virus derived from a fatally infected human. a control group of eight guinea-pigs was inoculated intraperitoneally with the same isolate in order to confirm virulence. three of eight infected guinea-pigs developed clinical signs 7-9 days post-inoculation. infected fruit bats developed a subclinical infection characterized by the transient presence of virus within selected viscera, ep ...200717498518
serine/threonine kinase dependent transcription from the polyhedrin promoter of spltnpv-i.polyhedrin (polh) and p10 are the two hyper-expressed very late genes of nucleopolyhedroviruses. alpha amanitin resistant transcription from spodoptera litura nucleopolyhedrovirus (spltnpv-i) polyhedrin promoter was observed with virus infected nuclear extract of niv-ha-197 cells but not with that from uninfected nuclear extract. anti-protein kinase-1 (pk1) antibody inhibited the transcription and the inhibition reversed on addition of pk1, however, pk1 mutant protein, k50m having no phosphoryla ...200717512903
risk of nosocomial transmission of nipah virus in a bangladesh hospital.we conducted a seroprevalence study and exposure survey of healthcare workers to assess the risk of nosocomial transmission of nipah virus during an outbreak in bangladesh in 2004. no evidence of recent nipah virus infection was detected despite substantial exposures and minimal use of personal protective equipment.200717520553
human neuronal cell protein responses to nipah virus infection.nipah virus (niv), a recently discovered zoonotic virus infects and replicates in several human cell types. its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. in the present study, the sk-n-mc human neuronal cell protein response to niv infection is examined using proteomic approaches.200717553172
recent progress in henipavirus research.following the discovery of two new paramyxoviruses in the 1990s, much effort has been placed on rapidly finding the reservoir hosts, characterising the genomes, identifying the viral receptors and formulating potential vaccines and therapeutic options for these viruses, hendra and nipah viruses caused zoonotic disease on a scale not seen before with other paramyxoviruses. nipah virus particularly caused high morbidity and mortality in humans and high morbidity in pig populations in the first out ...200717629946
molecular determinants of antiviral potency of paramyxovirus entry inhibitors.hendra virus (hev) and nipah virus (niv) constitute the henipavirus genus of paramyxoviruses, both fatal in humans and with the potential for subversion as agents of bioterrorism. binding of the hev/niv attachment protein (g) to its receptor triggers a series of conformational changes in the fusion protein (f), ultimately leading to formation of a postfusion six-helix bundle (6hb) structure and fusion of the viral and cellular membranes. the ectodomain of paramyxovirus f proteins contains two co ...200717652384
single amino acid changes in the nipah and hendra virus attachment glycoproteins distinguish ephrinb2 from ephrinb3 usage.the henipaviruses, nipah virus (niv) and hendra virus (hev), are lethal emerging paramyxoviruses. ephrinb2 and ephrinb3 have been identified as receptors for henipavirus entry. niv and hev share similar cellular tropisms and likely use an identical receptor set, although a quantitative comparison of receptor usage by niv and hev has not been reported. here we show that (i) soluble niv attachment protein g (sniv-g) bound to cell surface-expressed ephrinb3 with a 30-fold higher affinity than that ...200717652392
[expression of nipah virus structural proteins f1 and g and preparation of hyperimmune antisera against two proteins].the fusion protein (f) and attachment glycoprotein (g) of nipah virus (niv) are important for the virus to infect cells and induce protective immunity. in this study, the niv f1 and g gene fragments without the sequences of signal peptide and transmembrane domain were amplified by pcr, then cloned into e. coli expression vector pgex-6p-1 and modified baculovirus vector, respectively. after induction by iptg, niv f1 and g proteins were efficiently expressed in e. coli when analyzed by sds-page, b ...200717672307
long-term neurological and functional outcome in nipah virus infection.nipah virus (niv) is an emerging zoonosis. central nervous system disease frequently results in high case-fatality. long-term neurological assessments of survivors are limited. we assessed long-term neurologic and functional outcomes of 22 patients surviving niv illness in bangladesh.200717696217
cis-acting elements in the antigenomic promoter of nipah virus.genome synthesis in paramyxoviruses, including nipah virus (niv), is controlled by sequence elements that reside in the non-coding nucleotides at the 5'-trailer (3'-antigenomic) end that make up the antigenomic promoter (agp). using a chloramphenicol acetyl transferase-based plasmid-driven minigenome system, the terminal 96 nt of niv agp were first mutagenized in blocks of three hexamers to enable broad mapping of the minigenome functional regions. this was followed by further dissection of thes ...200717698665
in utero transmission of nipah virus: role played by pregnancy and vertical transmission in henipavirus epidemiology. 200717703408
vertical transmission and fetal replication of nipah virus in an experimentally infected cat.a female adult cat developed clinical disease 13 days after subcutaneous inoculation with nipah virus (niv) and was discovered to be pregnant at necropsy. viral genome was detected in a variety of specimens, including blood, serum, tonsil swabs, and urine, up to 3 days before the onset of disease. samples collected postmortem, including placenta, uterine fluid, and fetal tissues, were also positive for niv genome, and the placenta and uterine fluid contained high levels of recoverable virus. the ...200717703410
infection and disease in reservoir and spillover hosts: determinants of pathogen emergence.infection and disease in reservoir and spillover hosts determine patterns of infectious agent availability and opportunities for infection, which then govern the process of transmission between susceptible species. in this chapter, using the zoonotic agents hendra virus and nipah virus as examples, the pathogenesis of infection in various species including the wildlife reservoirs and domestic spillover hosts is reviewed with an emphasis on the aspects of pathogenesis which contribute to the diss ...200717848063
henipaviruses: emerging paramyxoviruses associated with fruit bats.two related, novel, zoonotic paramyxoviruses have been described recently. hendra virus was first reported in horses and thence humans in australia in 1994; nipah virus was first reported in pigs and thence humans in malaysia in 1998. human cases of nipah virus infection, apparently unassociated with infection in livestock, have been reported in bangladesh since 2001. species of fruit bats (genus pteropus) have been identified as natural hosts of both agents. anthropogenic changes (habitat loss, ...200717848064
[global threats from emerging viral diseases].emerging viral diseases are nothing new. smallpox probably reached europe from asia in the 5th century, and yellow fever emerged in the americas during the 16th century as a consequence of the african slave trade. dengue fever arose simultaneously in south-east asia, africa, and north america during the 18th century. in 1918-1919 the so-called spanish flu spread like wildfire through all five continents, killing between 25 and 40 million people. the second half of the 20th century saw the emerge ...200718666456
role of electron microscopy in nipah virus outbreak investigation and control.in 1998, a novel paramyxovirus (order mononegavirales, family paramyxoviridae, subfamily paramyxovirinae, genus henipavirus) emerged in peninsular malaysia causing fatal encephalitis in humans and severe respiratory illness with encephalitis in pigs. the virus was successfully isolated in cultured mammalian cells. transmission electron microscopy of infected tissue culture cells played a crucial role in the early preliminary identification of the causative agent of the outbreak. this in turn was ...200718705447
lessons from the nipah virus outbreak in malaysia.the nipah virus outbreak in malaysia (september 1998 to may 1999) resulted in 265 cases of acute encephalitis with 105 deaths, and near collapse of the billion-dollar pig-farming industry. because it was initially attributed to japanese encephalitis, early control measures were ineffective, and the outbreak spread to other parts of malaysia and nearby singapore. the isolation of the novel aetiological agent, the nipah virus (niv), from the cerebrospinal fluid of an outbreak victim was the turnin ...200719108397
public health awareness of emerging zoonotic viruses of bats: a european perspective.bats classified in the order chiroptera are the most abundant and widely distributed non-human mammalian species in the world. several bat species are reservoir hosts of zoonotic viruses and therefore can be a public health hazard. lyssaviruses of different genotypes have emerged from bats in america (genotype 1 rabies virus; rabv), europe (european bat lyssavirus; eblv), and australia (australian bat lyssavirus; ablv), whereas nipah virus is the most important recent zoonosis of bat origin in a ...200617187565
nipah virus-associated encephalitis outbreak, siliguri, india.during january and february 2001, an outbreak of febrile illness associated with altered sensorium was observed in siliguri, west bengal, india. laboratory investigations at the time of the outbreak did not identify an infectious agent. because siliguri is in close proximity to bangladesh, where outbreaks of nipah virus (niv) infection were recently described, clinical material obtained during the siliguri outbreak was retrospectively analyzed for evidence of niv infection. niv-specific immunogl ...200616494748
going to bat. 200616502604
hendra and nipah viruses: different and dangerous.hendra virus and nipah virus are highly pathogenic paramyxoviruses that have recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in australia, malaysia, singapore and bangladesh. their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. these features led to their classification into the new genus henipavirus within the family paramyxoviridae and to their designation as biosafety level 4 pathogens. t ...200616357858
foodborne transmission of nipah virus, bangladesh.we investigated an outbreak of encephalitis in tangail district, bangladesh. we defined case-patients as persons from the outbreak area in whom fever developed with new onset of seizures or altered mental status from december 15, 2004, through january 31, 2005. twelve persons met the definition; 11 (92%) died. serum specimens were available from 3; 2 had immunoglobulin m antibodies against nipah virus by capture enzyme immunoassay. we enrolled 11 case-patients and 33 neighborhood controls in a c ...200617326940
pulau virus; a new member of the nelson bay orthoreovirus species isolated from fruit bats in malaysia.after the outbreak of nipah virus (niv) in 1998-99, which resulted in 105 human deaths and the culling of more than one million pigs, a search was initiated for the natural host reservoir of niv on tioman island off the east coast of malaysia. three different syncytia-forming viruses were isolated from fruit bats on the island. they were nipah virus, tioman virus (a novel paramyxovirus related to menangle virus), and a reovirus, named pulau virus (puv), which is the subject of this study. puv di ...200616205863
production and characterization of monoclonal antibodies against binary ethylenimine inactivated nipah virus.nipah virus, a zoonotic paramyxovirus which emerged recently was chemically inactivated using binary ethylenimine (bei). the inactivated virus was concentrated and purified by sucrose gradient centrifugation. the gradient fractions were examined by electron microscopy and western immunoblot, and gradient fraction containing mainly nipah matrix (m) and nucleocapsid (n) proteins was used for immunizing balb/c mice to generate hybridomas. screening of the resultant hybridoma clones identified five ...200616226320
potent neutralization of hendra and nipah viruses by human monoclonal antibodies.hendra virus (hev) and nipah virus (niv) are closely related emerging viruses comprising the henipavirus genus of the paramyxovirinae. each has a broad species tropism and can cause disease with high mortality in both animal and human hosts. these viruses infect cells by a ph-independent membrane fusion event mediated by their attachment (g) and fusion (f) envelope glycoproteins (envs). seven fabs, m101 to -7, were selected for their significant binding to a soluble form of hendra g (sg) which w ...200616378991
antibody prophylaxis and therapy against nipah virus infection in hamsters.nipah virus (niv), a member of the paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. in humans, the infection leads to encephalitis with >40 to 70% mortality. we have previously shown that polyclonal antibody directed to either one of two glycoproteins, g (attachment protein) or f (fusion protein), can protect hamsters from a lethal infection. in the present study, we have developed monoclonal antib ...200616439553
developments towards effective treatments for nipah and hendra virus infection.hendra and nipah virus are closely related emerging viruses comprising the henipavirus genus of the subfamily paramyxovirinae and are distinguished by their ability to cause fatal disease in both animal and human hosts. in particular, the high mortality and person-to-person transmission associated with the most recent nipah virus outbreaks, as well as the very recent re-emergence of hendra virus, has confirmed the importance and necessity of developing effective therapeutic interventions. much r ...200616441208
development of human monoclonal antibodies against diseases caused by emerging and biodefense-related viruses.polyclonal antibodies have a century-old history of being effective against some viruses; recently, monoclonal antibodies (mabs) have also shown success. the humanized mab synagis (palivizumab), which is still the only mab against a viral disease approved by the us fda, has been widely used as a prophylactic measure against respiratory syncytial virus infections in neonates and immunocompromised individuals. the first fully human mabs against two other paramyxoviruses, hendra and nipah virus, wh ...200616441209
nipah virus: impact, origins, and causes of emergence.nipah virus is an emerging zoonotic pathogen that causes severe febrile encephalitis resulting in death in 40% to 75% of human cases. nipah virus is considered a biosafety level-4 pathogen and is listed as a select agent with high risk for public health and security due to its high mortality rate in people and the lack of effective vaccines or therapies. the natural reservoir for nipah virus and related members of the genus henipavirus are fruit bats of the genus pteropus. nipah virus emerged in ...200616448602
a mature and fusogenic form of the nipah virus fusion protein requires proteolytic processing by cathepsin l.the nipah virus fusion (f) protein is proteolytically processed to f1 + f2 subunits. we demonstrate here that cathepsin l is involved in this important maturation event. cathepsin inhibitors ablated cleavage of nipah f. proteolytic processing of nipah f and fusion activity was dramatically reduced in cathepsin l shrna-expressing vero cells. additionally, nipah virus f-mediated fusion was inhibited in cathepsin l-deficient cells, but coexpression of cathepsin l restored fusion activity. both puri ...200616460775
two key residues in ephrinb3 are critical for its use as an alternative receptor for nipah virus.ephrinb2 was recently discovered as a functional receptor for nipah virus (niv), a lethal emerging paramyxovirus. ephrins constitute a class of homologous ligands for the eph class of receptor tyrosine kinases and exhibit overlapping expression patterns. thus, we examined whether other ephrins might serve as alternative receptors for niv. here, we show that of all known ephrins (ephrina1-a5 and ephrinb1-b3), only the soluble fc-fusion proteins of ephrinb3, in addition to ephrinb2, bound to solub ...200616477309
the need for continuing vigilance: addressing the threat for transmission of blood-borne infectious disease.as international travel and human encroachment into previously isolated areas have increased, so too has the potential for the emergence of new infectious diseases. populations likely to be susceptible to new infectious diseases have also increased in size. the past three decades have seen outbreaks of diseases caused by parvoviruses, nipah virus, circoviruses, and prions. infectious pathogens such as these are formidable opponents; they can adapt to new hosts or cause variant diseases within ne ...200616631823
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