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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
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
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
epidemiological perspectives on hendra virus infection in horses and flying foxes. 200717615038
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
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
[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
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
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
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
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
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
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
antibodies to nipah or nipah-like viruses in bats, china. 200819046545
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
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
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
in-depth assessment of an outbreak of nipah encephalitis with person-to-person transmission in bangladesh: implications for prevention and control strategies.continued nipah encephalitis outbreaks in bangladesh highlight the need for preventative and control measures to reduce transmission from bats to humans and human-to-human spread. qualitative research was conducted at the end of an encephalitis outbreak in faridpur, bangladesh in may 2004 and continued through december 2004. methods included in-depth interviews with caretakers of cases, case survivors, neighbors of cases, and health providers. results show contrasts between local and biomedical ...200919141846
animal models for the study of emerging zoonotic viruses: nipah and hendra. 200919200760
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
clinical presentation of nipah virus infection in bangladesh.in bangladesh, 4 outbreaks of nipah virus infection were identified during the period 2001-2004.200818444812
[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
henipaviruses: a new family of emerging paramyxoviruses.paramyxoviruses have been implicated in both animal and human infections. some viruses, such as morbilliviruses are responsible for large-scale epidemics. however, there are limited observations of these viruses crossing the host species barrier in nature. in 1994, in australia a fatal infection in horses and humans was identified to be caused by a new paramyxovirus, hendra virus (hev), and in 1998 in malaysia, a closely related virus, nipah virus (niv) was responsible for fatal infections in pi ...200918511217
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
evidence of henipavirus infection in west african fruit bats.henipaviruses are emerging rna viruses of fruit bat origin that can cause fatal encephalitis in man. ghanaian fruit bats (megachiroptera) were tested for antibodies to henipaviruses. using a luminex multiplexed microsphere assay, antibodies were detected in sera of eidolon helvum to both nipah (39%, 95% confidence interval: 27-51%) and hendra (22%, 95% ci: 11-33%) viruses. virus neutralization tests further confirmed seropositivity for 30% (7/23) of luminex positive serum samples. our results in ...200818648649
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
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
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
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
reproduction and nutritional stress are risk factors for hendra virus infection in little red flying foxes (pteropus scapulatus).hendra virus (hev) is a lethal paramyxovirus which emerged in humans in 1994. poor understanding of hev dynamics in pteropus spp. (flying fox or fruit bat) reservoir hosts has limited our ability to determine factors driving its emergence. we initiated a longitudinal field study of hev in little red flying foxes (lrff; pteropus scapulatus) and examined individual and population risk factors for infection, to determine probable modes of intraspecific transmission. we also investigated whether sea ...200818198149
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
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
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
animal models of henipavirus infection: a review.hendra virus (hev) and nipah virus (niv) form a separate genus henipavirus within the family paramyxoviridae, and are classified as biosafety level four 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 20th century, causing severe disease in humans, horses and swine, and infecting a number of other mammalian species. the current review ...200919084436
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
determination of the henipavirus phosphoprotein gene mrna editing frequencies and detection of the c, v and w proteins of nipah virus in virus-infected cells.the henipaviruses, nipah virus (niv) and hendra virus (hev), are highly pathogenic zoonotic paramyxoviruses. like many other paramyxoviruses, henipaviruses employ a process of 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 alternate reading frame. sequence analysis of multiple, cloned mrnas showed that the mrna editing frequencies of the p genes ...200919141449
simulating henipavirus multicycle replication in a screening assay leads to identification of a promising candidate for therapy.nipah (niv) and hendra (hev) viruses are emerging zoonotic paramyxoviruses that cause encephalitis in humans, with fatality rates of up to 75%. we designed a new high-throughput screening (hts) assay for inhibitors of infection based on envelope glycoprotein pseudotypes. the assay simulates multicycle replication and thus identifies inhibitors that target several stages of the viral life cycle, but it still can be carried out under biosafety level 2 (bsl-2) conditions. these features permit a sc ...200919264786
establishment, immortalisation and characterisation of pteropid bat cell lines.bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including nipah virus, hendra virus, severe acute respiratory syndrome coronavirus and ebola virus. since the discovery of sars-like coronaviruses in chinese horseshoe bats, attempts to isolate a sl-cov from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. new stable bat cell lines are needed to help with these investig ...200920011515
acute hendra virus infection: analysis of the pathogenesis and passive antibody protection in the hamster model.hendra virus (hev) and nipah virus (niv) are recently-emerged, closely related and highly pathogenic paramyxoviruses. we have analysed here the pathogenesis of the acute hev infection using the new animal model, golden hamster (mesocricetus auratus), which is highly susceptible to hev infection. hev-specific rna and viral antigens were found in multiple organs and virus was isolated from different tissues. dual pathogenic mechanism was observed: parenchymal infection in various organs, including ...200919328514
hendra virus outbreak with novel clinical features, australia.to determine the epidemiologic and clinical features of a 2008 outbreak of hendra virus infection in a veterinary clinic in australia, we investigated the equine case-series. four of 5 infected horses died, as did 1 of 2 infected staff members. clinical manifestation in horses was predominantly neurologic. preclinical transmission appears likely.201020113576
a longitudinal study of the prevalence of nipah virus in pteropus lylei bats in thailand: evidence for seasonal preference in disease transmission.after 12 serial nipah virus outbreaks in humans since 1998, it has been noted that all except the initial event in malaysia occurred during the first 5 months of the year. increasingly higher morbidity and mortality have been observed in subsequent outbreaks in india and bangladesh. this may have been related to different virus strains and transmission capability from bat to human without the need for an amplifying host and direct human-to-human transmission. a survey of virus strains in pteropu ...201019402762
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
targeted strategies for henipavirus therapeutics.hendra and nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. the high case fatality and person-to-person transmission associated with the most recent niv outbreaks, and the recent re-emergence of hev, emphasize the importance and necessity of effective therapeutics for these novel agents. in recent ye ...200719440455
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
design and evaluation of consensus pcr assays for henipaviruses.henipaviruses were first discovered in the 1990s, and their potential threat to public health is of increasing concern with increasing knowledge. old-world fruit bats are the reservoir hosts for these viruses, and spill-over events cause lethal infections in a wide range of mammalian species, including humans. in anticipation of these spill-over events, and to investigate further the geographical range of these genetically diverse viruses, assays for detection of known and potentially novel stra ...200919477200
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
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
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
emerging epidemic viral encephalitides with a special focus on henipaviruses.in the last few decades, there is an increasing emergence and re-emergence of viruses, such as west nile virus, enterovirus 71 and henipaviruses that cause epidemic viral encephalitis and other central nervous system (cns) manifestations. the mortality and morbidity associated with these outbreaks are significant and frequently severe. while aspects of epidemiology, basic virology, etc., may be known, the pathology and pathogenesis are often less so, partly due to a lack of interest among pathol ...201020652579
[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
residues in the stalk domain of the hendra virus g glycoprotein modulate conformational changes associated with receptor binding.hendra virus (hev) is a member of the broadly tropic and highly pathogenic paramyxovirus genus henipavirus. hev is enveloped and infects cells by using membrane-anchored attachment (g) and fusion (f) glycoproteins. g possesses an n-terminal cytoplasmic tail, an external membrane-proximal stalk domain, and a c-terminal globular head that binds the recently identified receptors ephrinb2 and ephrinb3. receptor binding is presumed to induce conformational changes in g that subsequently trigger f-med ...200818799571
a novel model of lethal hendra virus infection in african green monkeys and the effectiveness of ribavirin treatment.the henipaviruses, hendra virus (hev) and nipah virus (niv), are emerging zoonotic paramyxoviruses that can cause severe and often lethal neurologic and/or respiratory disease in a wide variety of mammalian hosts, including humans. there are presently no licensed vaccines or treatment options approved for human or veterinarian use. guinea pigs, hamsters, cats, and ferrets, have been evaluated as animal models of human hev infection, but studies in nonhuman primates (nhp) have not been reported, ...201020660198
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
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
[nipah virus (niv)]. 201020942075
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
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
combined chloroquine and ribavirin treatment does not prevent death in a hamster model of nipah and hendra virus infection.hendra virus (hev) and nipah virus (niv) are recently emerged, closely related and highly pathogenic paramyxoviruses that cause severe disease such as encephalitis in animals and humans with fatality rates of up to 75 %. due to their high case fatality rate following human infection and because of the lack of effective vaccines or therapy, they are classified as biosafety level 4 pathogens. a recent study reported that chloroquine, an anti-malarial drug, was effective in preventing niv and hev i ...201019889926
organ- and endotheliotropism of nipah virus infections in vivo and in vitro.nipah virus (niv) is a highly pathogenic paramyxovirus that was first isolated in 1999 during an outbreak in malaysia. in contrast to other paramyxoviruses niv infects many mammalian species. because of its zoonotic potential, the high pathogenicity and the lack of therapeutic treatment, niv was classified as a biosafety level 4 pathogen. in humans niv causes a severe acute encephalitis whereas in some animal hosts respiratory symptoms are predominantly observed. despite the differences in the c ...200919967130
characterization of nipah virus from naturally infected pteropus vampyrus bats, malaysia.we isolated and characterized nipah virus (niv) from pteropus vampyrus bats, the putative reservoir for the 1998 outbreak in malaysia, and provide evidence of viral recrudescence. this isolate is monophyletic with previous nivs in combined analysis, and the nucleocapsid gene phylogeny species.201021122240
prevalence of henipavirus and rubulavirus antibodies in pteropid bats, papua new guinea.to determine seroprevalence of viruses in bats in papua new guinea, we sampled 66 bats at 3 locations. we found a seroprevalence of 55% for henipavirus (hendra or nipah virus) and 56% for rubulavirus (tioman or menangle virus). notably, 36% of bats surveyed contained antibodies to both types of viruses, indicating concurrent or consecutive infection.201021122242
human hendra virus encephalitis associated with equine outbreak, australia, 2008.a recent hendra virus outbreak at a veterinary clinic in brisbane, queensland, australia, involved 5 equine and 2 human infections. in contrast to previous outbreaks, infected horses had predominantly encephalitic, rather than respiratory, signs. after an incubation period of 9-16 days, influenza-like illnesses developed in the 2 persons before progressing to encephalitis; 1 died. both patients were given ribavirin. basal serum and cerebrospinal fluid levels were 10-13 mg/l after intravenous adm ...201020113550
experimental infection of squirrel monkeys with nipah virus.we infected squirrel monkeys (saimiri sciureus) with nipah virus to determine the monkeys' suitability for use as primate models in preclinical testing of preventive and therapeutic treatments. infection of squirrel monkeys through intravenous injection was followed by high death rates associated with acute neurologic and respiratory illness and viral rna and antigen production.201020202432
nipah virus fact sheet (revised in july 2009). 201020210044
quantification of the severity of an outbreak in human infection control.the severity of an outbreak is a priority in decision-making for human infection control. however, there have been no reports on how to quantify the severity of an outbreak.201020227902
dimeric architecture of the hendra virus attachment glycoprotein: evidence for a conserved mode of assembly.hendra virus is a negative-sense single-stranded rna virus within the paramyxoviridae family which, together with nipah virus, forms the henipavirus genus. infection with bat-borne hendra virus leads to a disease with high mortality rates in humans. we determined the crystal structure of the unliganded six-bladed beta-propeller domain and compared it to the previously reported structure of hendra virus attachment glycoprotein (hev-g) in complex with its cellular receptor, ephrin-b2. as observed ...201020375167
nipah virus outbreak with person-to-person transmission in a district of bangladesh, 2007.in february 2007 an outbreak of nipah virus (niv) encephalitis in thakurgaon district of northwest bangladesh affected seven people, three of whom died. all subsequent cases developed illness 7-14 days after close physical contact with the index case while he was ill. cases were more likely than controls to have been in the same room (100% vs. 9.5%, or undefined, p<0.001) and to have touched him (83% vs. 0%, or undefined, p<0.001). although the source of infection for the index case was not iden ...201020380769
development of an acute and highly pathogenic nonhuman primate model of nipah virus infection.nipah virus (niv) is an enigmatic emerging pathogen 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 percent and there are no vaccines or treatments approved for human use. guinea pigs, hamsters, cats, ferrets, pigs and most recently squirrel monkeys (new world monkey) have been evaluated as animal models of human niv infection, and with the exception of the ferret, no model recapitula ...201020502528
risk factors, prevention and communication strategy during nipah virus outbreak in malaysia.an outbreak of acute febrile encephalitis affecting pig-farm workers and owners was recognized in peninsular malaysia as early as september 1998. the outbreak was initially thought to be due to japanese encephalitis (je) virus and thus very intensive prevention, control and communication strategies directed at je virus were undertaken by the ministry of health and ministry of agriculture of malaysia. there was an immediate change in the prevention, control and communication strategies with focus ...201021329177
emerging paramyxoviruses: molecular mechanisms and antiviral strategies.in recent years, several paramyxoviruses have emerged to infect humans, including previously unidentified zoonoses. hendra and nipah viruses (henipaviruses within this family) were first identified in the 1990s in australia, malaysia and singapore, causing epidemics with high mortality and morbidity rates in affected animals and humans. other paramyxoviruses, such as menangle virus, tioman virus, human metapneumovirus and avian paramyxovirus 1, which cause less morbidity in humans, have also bee ...201121345285
epidemiology. breaking the chain in bangladesh. 201121385693
use of monoclonal antibodies against hendra and nipah viruses in an antigen capture elisa.outbreaks of hendra (hev) and nipah (niv) viruses have been reported starting in 1994 and 1998, respectively. both viruses are capable of causing fatal disease in humans and effecting great economical loss in the livestock industry.201020525276
date palm sap collection: exploring opportunities to prevent nipah transmission.nipah virus (niv) infection is a seasonal disease in bangladesh that coincides with the date palm sap collection season. raw date palm sap is a delicacy to drink in bengali culture. if fruit bats that are infected with niv gain access to the sap for drinking, they might occasionally contaminate the sap through saliva and urine. in february 2007, we conducted a qualitative study in six villages, interviewing 27 date palm sap collectors (gachhis) within the geographical area where niv outbreaks ha ...201020617362
bats without borders: long-distance movements and implications for disease risk management.fruit bats of the genus pteropus (commonly known as flying-foxes) are the natural hosts of several recently emerged zoonotic viruses of animal and human health significance in australia and asia, including hendra and nipah viruses. satellite telemetry was used on nine flying-foxes of three species (pteropus alecto n=5, p. vampyrus n=2, and p. neohibernicus n=2) to determine the scale and pattern of their long-distance movements and their potential to transfer these viruses between countries in t ...201020645122
endothelial galectin-1 binds to specific glycans on nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation.nipah virus targets human endothelial cells via niv-f and niv-g envelope glycoproteins, resulting in endothelial syncytia formation and vascular compromise. endothelial cells respond to viral infection by releasing innate immune effectors, including galectins, which are secreted proteins that bind to specific glycan ligands on cell surface glycoproteins. we demonstrate that galectin-1 reduces niv-f mediated fusion of endothelial cells, and that endogenous galectin-1 in endothelial cells is suffi ...201020657665
structural disorder within henipavirus nucleoprotein and phosphoprotein: from predictions to experimental assessment.henipaviruses are newly emerged viruses within the paramyxoviridae family. their negative-strand rna genome is packaged by the nucleoprotein (n) within alpha-helical nucleocapsid that recruits the polymerase complex made of the l protein and the phosphoprotein (p). to date structural data on henipaviruses are scarce, and their n and p proteins have never been characterized so far. using both computational and experimental approaches we herein show that henipaviruses n and p proteins possess larg ...201020657787
genomic characterization of nipah virus, west bengal, india.an intrafamilial outbreak in west bengal, india, involving 5 deaths and person-to-person transmission was attributed to nipah virus. full-genome sequence of nipah virus (18,252 nt) amplified from lung tissue showed 99.2% nt and 99.8% aa identity with the bangladesh-2004 isolate, suggesting a common source of the virus.201121529409
off label antiviral therapeutics for henipaviruses: new light through old windows.hendra and nipah viruses are recently emerged zoonotic paramyxoviruses for which there is no vaccine or protective therapy available. while a number of experimental therapeutics and vaccines have recently been reported, all of these will require lengthy approval processes, limiting their usefulness in the short term. to address the urgent need for henipavirus therapeutics, a number of currently licensed pharmaceuticals have been evaluated for off label efficacy against henipavirus replication in ...201020668647
screening for nipah virus infection in west kalimantan province, indonesia.compared to other viruses, research on nipah virus has been limited in indonesia because attributable disease outbreaks have not been reported. however, nipah virus is a zoonotic biosafety level 4 (bsl4) agent, so strategic monitoring is prudent. farmer interviews and a serologic survey of 610 pig sera and 99 bat sera from west kalimantan province were conducted. farmers reported no recent or historic encephalitic or respiratory disease in themselves, their families, workers or pigs. the survey ...201019638160
a catalytically and genetically optimized beta-lactamase-matrix based assay for sensitive, specific, and higher throughput analysis of native henipavirus entry characteristics.nipah virus (niv) and hendra virus (hev) are the only paramyxoviruses requiring biosafety level 4 (bsl-4) containment. thus, study of henipavirus entry at less than bsl-4 conditions necessitates the use of cell-cell fusion or pseudotyped reporter virus assays. yet, these surrogate assays may not fully emulate the biological properties unique to the virus being studied. thus, we developed a henipaviral entry assay based on a beta-lactamase-nipah matrix (betala-m) fusion protein. we first codon-op ...200919646266
production of the matrix protein of nipah virus in escherichia coli: virus-like particles and possible application for diagnosis.the broad species tropism of nipah virus (niv) coupled with its high pathogenicity demand a rapid search for a new biomarker candidate for diagnosis. the matrix (m) protein was expressed in escherichia coli and purified using a ni-nta affinity column chromatography and sucrose density gradient centrifugation. the recombinant m protein with the molecular mass (mr) of about 43 kda was detected by anti-niv serum and anti-myc antibody. about 50% of the m protein was found to be soluble and localized ...200919666056
induction of neutralizing antibodies to hendra and nipah glycoproteins using a venezuelan equine encephalitis virus in vivo expression system.the emergence of hendra virus (hev) and nipah virus (niv) which can cause fatal infections in both animals and humans has triggered a search for an effective vaccine. here, we have explored the potential for generating an effective humoral immune response to these zoonotic pathogens using an alphavirus-based vaccine platform. groups of mice were immunized with venezuelan equine encephalitis virus replicon particles (vrps) encoding the attachment or fusion glycoproteins of either hev or niv. we d ...201021050901
inhibition of nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.in the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (f) leading to viral and cellular membrane fusion. peptides derived from c-terminal heptad repeat (hrc) regions in f have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. we recently showed that the addition of a cholesterol group to hrc peptides active against nipah virus targets these peptides to the membrane where fusion occurs, dramatically in ...201021060819
a functional henipavirus envelope glycoprotein pseudotyped lentivirus assay system.hendra virus (hev) and nipah virus (niv) are newly emerged zoonotic paramyxoviruses discovered during outbreaks in queensland, australia in 1994 and peninsular malaysia in 1998/9 respectively and classified within the new henipavirus genus. both viruses can infect a broad range of mammalian species causing severe and often-lethal disease in humans and animals, and repeated outbreaks continue to occur. extensive laboratory studies on the host cell infection stage of hev and niv and the roles of t ...201021073718
ubiquitin-regulated nuclear-cytoplasmic trafficking of the nipah virus matrix protein is important for viral budding.paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associated with this nuclear localization remains obscure. we report here that the nuclear-cytoplasmic trafficking of the nipah virus matrix (niv-m) protein and associated post-translationa ...201021085610
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