Displaying publications 41 - 60 of 133 in total

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  1. Eaton BT, Broder CC, Wang LF
    Curr Mol Med, 2005 Dec;5(8):805-16.
    PMID: 16375714
    Within the past decade a number of new zoonotic paramyxoviruses emerged from flying foxes to cause serious disease outbreaks in man and livestock. Hendra virus was the cause of fatal infections of horses and man in Australia in 1994, 1999 and 2004. Nipah virus caused encephalitis in humans both in Malaysia in 1998/99, following silent spread of the virus in the pig population, and in Bangladesh from 2001 to 2004 probably as a result of direct bat to human transmission and spread within the human population. Hendra and Nipah viruses are highly pathogenic in humans with case fatality rates of 40% to 70%. Their genetic constitution, virulence and wide host range make them unique paramyxoviruses and they have been given Biosecurity Level 4 status in a new genus Henipavirus within the family Paramyxoviridae. Recent studies on the virulence, host range and cell tropisms of henipaviruses provide insights into the unique biological properties of these emerging human pathogens and suggest approaches for vaccine development and therapeutic countermeasures.
    Matched MeSH terms: Henipavirus Infections/epidemiology; Henipavirus Infections/therapy*; Henipavirus Infections/virology*
  2. Eaton BT, Broder CC, Middleton D, Wang LF
    Nat Rev Microbiol, 2006 Jan;4(1):23-35.
    PMID: 16357858
    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. This review provides an overview of henipaviruses and the types of infection they cause, and describes how studies on the structure and function of henipavirus proteins expressed from cloned genes have provided insights into the unique biological properties of these emerging human pathogens.
    Matched MeSH terms: Henipavirus Infections/etiology; Henipavirus Infections/immunology; Henipavirus Infections/virology
  3. Simons RR, Gale P, Horigan V, Snary EL, Breed AC
    Viruses, 2014 May 16;6(5):2084-121.
    PMID: 24841385 DOI: 10.3390/v6052084
    Bat-borne viruses can pose a serious threat to human health, with examples including Nipah virus (NiV) in Bangladesh and Malaysia, and Marburg virus (MARV) in Africa. To date, significant human outbreaks of such viruses have not been reported in the European Union (EU). However, EU countries have strong historical links with many of the countries where NiV and MARV are present and a corresponding high volume of commercial trade and human travel, which poses a potential risk of introduction of these viruses into the EU. In assessing the risks of introduction of these bat-borne zoonotic viruses to the EU, it is important to consider the location and range of bat species known to be susceptible to infection, together with the virus prevalence, seasonality of viral pulses, duration of infection and titre of virus in different bat tissues. In this paper, we review the current scientific knowledge of all these factors, in relation to the introduction of NiV and MARV into the EU.
    Matched MeSH terms: Henipavirus Infections/epidemiology*; Henipavirus Infections/transmission; Henipavirus Infections/veterinary*
  4. Ong KC, Wong KT
    Brain Pathol, 2015 Sep;25(5):605-13.
    PMID: 26276024 DOI: 10.1111/bpa.12278
    The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future.
    Matched MeSH terms: Henipavirus Infections/diagnosis*; Henipavirus Infections/pathology; Henipavirus Infections/therapy
  5. Eshaghi M, Tan WS, Ong ST, Yusoff K
    J Clin Microbiol, 2005 Jul;43(7):3172-7.
    PMID: 16000431
    The nucleocapsid (N) protein of Nipah virus (NiV) is a major constituent of the viral proteins which play a role in encapsidation, regulating the transcription and replication of the viral genome. To investigate the use of a fusion system to aid the purification of the recombinant N protein for structural studies and potential use as a diagnostic reagent, the NiV N gene was cloned into the pFastBacHT vector and the His-tagged fusion protein was expressed in Sf9 insect cells by recombinant baculovirus. Western blot analysis of the recombinant fusion protein with anti-NiV antibodies produced a band of approximately 62 kDa. A time course study showed that the highest level of expression was achieved after 3 days of incubation. Electron microscopic analysis of the NiV recombinant N fusion protein purified on a nickel-nitrilotriacetic acid resin column revealed different types of structures, including spherical, ring-like, and herringbone-like particles. The light-scattering measurements of the recombinant N protein also confirmed the polydispersity of the sample with hyrdrodynamic radii of small and large types. The optical density spectra of the purified recombinant fusion protein revealed a high A(260)/A(280) ratio, indicating the presence of nucleic acids. Western blotting and enzyme-linked immunosorbent assay results showed that the recombinant N protein exhibited the antigenic sites and conformation necessary for specific antigen-antibody recognition.
    Matched MeSH terms: Henipavirus Infections/diagnosis; Henipavirus Infections/veterinary; Henipavirus Infections/virology
  6. Kaku Y, Park ES, Noguchi A, Inoue S, Lunt R, Malbas FF, et al.
    J Virol Methods, 2019 07;269:83-87.
    PMID: 30954461 DOI: 10.1016/j.jviromet.2019.03.009
    A novel indirect fluorescent antibody test (IFAT) for detection of IgM against Nipah virus (NiV) was developed using HeLa 229 cells expressing recombinant NiV nucleocapsid protein (NiV-N). The NiV IFAT was evaluated using three panels of sera: a) experimentally produced sera from NiV-N-immunized/pre-immunized macaques, b) post-infection human sera associated with a Nipah disease outbreak in the Philippines in 2014, and c) human sera from a non-exposed Malaysian population. Immunized macaque sera showed a characteristic granular staining pattern of the NiV-N expressed antigen in HeLa 229 cells, which was readily distinguished from negative-binding results of the pre-immunized macaque sera. The IgM antibody titers in sequential serum samples (n = 7) obtained from three Nipah patients correlated well with previously published results using conventional IgM capture ELISA and SNT serology. The 90 human serum samples from unexposed persons were unreactive by IFAT. The IFAT utilizing NiV-N-expressing HeLa 229 cells to detect IgM antibody in an early stage of NiV infection is an effective approach, which could be utilized readily in local laboratories to complement other capabilities in NiV-affected countries.
    Matched MeSH terms: Henipavirus Infections/blood; Henipavirus Infections/diagnosis*; Henipavirus Infections/immunology
  7. Johnston SC, Briese T, Bell TM, Pratt WD, Shamblin JD, Esham HL, et al.
    PLoS One, 2015;10(2):e0117817.
    PMID: 25706617 DOI: 10.1371/journal.pone.0117817
    Henipaviruses are implicated in severe and frequently fatal pneumonia and encephalitis in humans. There are no approved vaccines or treatments available for human use, and testing of candidates requires the use of well-characterized animal models that mimic human disease. We performed a comprehensive and statistically-powered evaluation of the African green monkey model to define parameters critical to disease progression and the extent to which they correlate with human disease. African green monkeys were inoculated by the intratracheal route with 2.5 × 10(4) plaque forming units of the Malaysia strain of Nipah virus. Physiological data captured using telemetry implants and assessed in conjunction with clinical pathology were consistent with shock, and histopathology confirmed widespread tissue involvement associated with systemic vasculitis in animals that succumbed to acute disease. In addition, relapse encephalitis was identified in 100% of animals that survived beyond the acute disease phase. Our data suggest that disease progression in the African green monkey is comparable to the variable outcome of Nipah virus infection in humans.
    Matched MeSH terms: Henipavirus Infections/pathology*; Henipavirus Infections/virology*
  8. Dups J, Middleton D, Long F, Arkinstall R, Marsh GA, Wang LF
    Virol J, 2014;11:102.
    PMID: 24890603 DOI: 10.1186/1743-422X-11-102
    Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis.
    Matched MeSH terms: Henipavirus Infections/pathology*; Henipavirus Infections/virology*
  9. Aguilar HC, Lee B
    Expert Rev Mol Med, 2011;13:e6.
    PMID: 21345285 DOI: 10.1017/S1462399410001754
    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 been recently identified. Although the Paramyxoviridae family of viruses has been previously recognised as biomedically and veterinarily important, the recent emergence of these paramyxoviruses has focused our attention on this family. Antiviral drugs can be designed to target specific important determinants of the viral life cycle. Therefore, identifying and understanding the mechanistic underpinnings of viral entry, replication, assembly and budding will be critical in the development of antiviral therapeutic agents. This review focuses on the molecular mechanisms discovered and the antiviral strategies pursued in recent years for emerging paramyxoviruses, with particular emphasis on viral entry and exit mechanisms.
    Matched MeSH terms: Henipavirus Infections/drug therapy*; Henipavirus Infections/epidemiology
  10. Chua KB, Wong EM, Cropp BC, Hyatt AD
    Med J Malaysia, 2007 Jun;62(2):139-42.
    PMID: 18705447 MyJurnal
    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 pivotal to determine the correct direction of control measures that subsequently brought the epidemic under control. In light of this investigation, and indeed identification of infectious agents associated with other disease episodes, electron microscopy will remain an important frontline method for rapid diagnostic virology and investigation of any future outbreak of new and unusual cases of illness suspected of an infectious aetiology.
    Matched MeSH terms: Henipavirus Infections/diagnosis; Henipavirus Infections/epidemiology*
  11. Choi C
    Sci. Am., 2004 Sep;291(3):21A, 22.
    PMID: 15376742
    Matched MeSH terms: Henipavirus Infections/epidemiology; Henipavirus Infections/transmission*
  12. Broder CC, Weir DL, Reid PA
    Vaccine, 2016 06 24;34(30):3525-34.
    PMID: 27154393 DOI: 10.1016/j.vaccine.2016.03.075
    Hendra virus (HeV) and Nipah virus (NiV) are zoonotic viruses that emerged in the mid to late 1990s causing disease outbreaks in livestock and people. HeV appeared in Queensland, Australia in 1994 causing a severe respiratory disease in horses along with a human case fatality. NiV emerged a few years later in Malaysia and Singapore in 1998-1999 causing a large outbreak of encephalitis with high mortality in people and also respiratory disease in pigs which served as amplifying hosts. The key pathological elements of HeV and NiV infection in several species of mammals, and also in people, are a severe systemic and often fatal neurologic and/or respiratory disease. In people, both HeV and NiV are also capable of causing relapsed encephalitis following recovery from an acute infection. The known reservoir hosts of HeV and NiV are several species of pteropid fruit bats. Spillovers of HeV into horses continue to occur in Australia and NiV has caused outbreaks in people in Bangladesh and India nearly annually since 2001, making HeV and NiV important transboundary biological threats. NiV in particular possesses several features that underscore its potential as a pandemic threat, including its ability to infect humans directly from natural reservoirs or indirectly from other susceptible animals, along with a capacity of limited human-to-human transmission. Several HeV and NiV animal challenge models have been developed which have facilitated an understanding of pathogenesis and allowed for the successful development of both active and passive immunization countermeasures.
    Matched MeSH terms: Henipavirus Infections/prevention & control*; Henipavirus Infections/veterinary
  13. Griffin BD, Leung A, Chan M, Warner BM, Ranadheera C, Tierney K, et al.
    Sci Rep, 2019 08 01;9(1):11171.
    PMID: 31371748 DOI: 10.1038/s41598-019-47549-y
    Nipah virus (NiV) has emerged as a highly lethal zoonotic paramyxovirus that is capable of causing a febrile encephalitis and/or respiratory disease in humans for which no vaccines or licensed treatments are currently available. There are two genetically and geographically distinct lineages of NiV: NiV-Malaysia (NiV-M), the strain that caused the initial outbreak in Malaysia, and NiV-Bangladesh (NiV-B), the strain that has been implicated in subsequent outbreaks in India and Bangladesh. NiV-B appears to be both more lethal and have a greater propensity for person-to-person transmission than NiV-M. Here we describe the generation and characterization of stable RNA polymerase II-driven infectious cDNA clones of NiV-M and NiV-B. In vitro, reverse genetics-derived NiV-M and NiV-B were indistinguishable from a wildtype isolate of NiV-M, and both viruses were pathogenic in the Syrian hamster model of NiV infection. We also describe recombinant NiV-M and NiV-B with enhanced green fluorescent protein (EGFP) inserted between the G and L genes that enable rapid and sensitive detection of NiV infection in vitro. This panel of molecular clones will enable studies to investigate the virologic determinants of henipavirus pathogenesis, including the pathogenic differences between NiV-M and NiV-B, and the high-throughput screening of candidate therapeutics.
    Matched MeSH terms: Henipavirus Infections/transmission; Henipavirus Infections/virology
  14. Rahman MZ, Islam MM, Hossain ME, Rahman MM, Islam A, Siddika A, et al.
    Int J Infect Dis, 2021 Jan;102:144-151.
    PMID: 33129964 DOI: 10.1016/j.ijid.2020.10.041
    BACKGROUND: Nipah virus (NiV) infection, often fatal in humans, is primarily transmitted in Bangladesh through the consumption of date palm sap contaminated by Pteropus bats. Person-to-person transmission is also common and increases the concern of large outbreaks. This study aimed to characterize the molecular epidemiology, phylogenetic relationship, and the evolution of the nucleocapsid gene (N gene) of NiV.

    METHODS: We conducted molecular detection, genetic characterization, and Bayesian time-scale evolution analyses of NiV using pooled Pteropid bat roost urine samples from an outbreak area in 2012 and archived RNA samples from NiV case patients identified during 2012-2018 in Bangladesh.

    RESULTS: NiV-RNA was detected in 19% (38/456) of bat roost urine samples and among them; nine N gene sequences were recovered. We also retrieved sequences from 53% (21 out of 39) of archived RNA samples from patients. Phylogenetic analysis revealed that all Bangladeshi strains belonged to NiV-BD genotype and had an evolutionary rate of 4.64 × 10-4 substitutions/site/year. The analyses suggested that the strains of NiV-BD genotype diverged during 1995 and formed two sublineages.

    CONCLUSION: This analysis provides further evidence that the NiV strains of the Malaysian and Bangladesh genotypes diverged recently and continue to evolve. More extensive surveillance of NiV in bats and human will be helpful to explore strain diversity and virulence potential to infect humans through direct or person-to-person virus transmission.

    Matched MeSH terms: Henipavirus Infections/epidemiology; Henipavirus Infections/virology*
  15. Clayton BA
    Curr Opin Virol, 2017 Feb;22:97-104.
    PMID: 28088124 DOI: 10.1016/j.coviro.2016.12.003
    Nipah virus is a recently-recognised, zoonotic paramyxovirus that causes severe disease and high fatality rates in people. Outbreaks have occurred in Malaysia, Singapore, India and Bangladesh, and a putative Nipah virus was also recently associated with human disease in the Philippines. Worryingly, human-to-human transmission is common in Bangladesh, where outbreaks occur with near-annual frequency. Onward human transmission of Nipah virus in Bangladesh is associated with close contact with clinically-unwell patients or their infectious secretions. While Nipah virus isolates associated with outbreaks of human infection have not resulted in sustained transmission to date, specific exposures carry a high risk of person-to-person transmission, an observation which is supported by recent findings in animal models. Novel paramyxoviruses continue to emerge from wildlife hosts, and represent an ongoing threat to human health globally.
    Matched MeSH terms: Henipavirus Infections/epidemiology; Henipavirus Infections/transmission*
  16. Yu J, Lv X, Yang Z, Gao S, Li C, Cai Y, et al.
    Viruses, 2018 10 19;10(10).
    PMID: 30347642 DOI: 10.3390/v10100572
    Nipah disease is a highly fatal zoonosis which is caused by the Nipah virus. The Nipah virus is a BSL-4 virus with fruit bats being its natural host. It is mainly prevalent in Southeast Asia. The virus was first discovered in 1997 in Negeri Sembilan, Malaysia. Currently, it is mainly harmful to pigs and humans with a high mortality rate. This study describes the route of transmission of the Nipah virus in different countries and analyzes the possibility of the primary disease being in China and the method of its transmission to China. The risk factors are analyzed for different susceptible populations to Nipah disease. The aim is to improve people's risk awareness and prevention and control of the disease and reduce its risk of occurring and spreading in China.
    Matched MeSH terms: Henipavirus Infections/epidemiology*; Henipavirus Infections/virology*
  17. Lee JH, Hammoud DA, Cong Y, Huzella LM, Castro MA, Solomon J, et al.
    J Infect Dis, 2020 05 11;221(Suppl 4):S419-S430.
    PMID: 31687756 DOI: 10.1093/infdis/jiz502
    Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 μm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.
    Matched MeSH terms: Henipavirus Infections/pathology; Henipavirus Infections/virology*
  18. Prasad AN, Woolsey C, Geisbert JB, Agans KN, Borisevich V, Deer DJ, et al.
    J Infect Dis, 2020 05 11;221(Suppl 4):S436-S447.
    PMID: 32022850 DOI: 10.1093/infdis/jiz613
    BACKGROUND: The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are capable of causing severe and often lethal respiratory and/or neurologic disease in animals and humans. Given the sporadic nature of henipavirus outbreaks, licensure of vaccines and therapeutics for human use will likely require demonstration of efficacy in animal models that faithfully reproduce the human condition. Currently, the African green monkey (AGM) best mimics human henipavirus-induced disease.

    METHODS: The pathogenic potential of HeV and both strains of NiV (Malaysia, Bangladesh) was assessed in cynomolgus monkeys and compared with henipavirus-infected historical control AGMs. Multiplex gene and protein expression assays were used to compare host responses.

    RESULTS: In contrast to AGMs, in which henipaviruses cause severe and usually lethal disease, HeV and NiVs caused only mild or asymptomatic infections in macaques. All henipaviruses replicated in macaques with similar kinetics as in AGMs. Infection in macaques was associated with activation and predicted recruitment of cytotoxic CD8+ T cells, Th1 cells, IgM+ B cells, and plasma cells. Conversely, fatal outcome in AGMs was associated with aberrant innate immune signaling, complement dysregulation, Th2 skewing, and increased secretion of MCP-1.

    CONCLUSION: The restriction factors identified in macaques can be harnessed for development of effective countermeasures against henipavirus disease.

    Matched MeSH terms: Henipavirus Infections/veterinary*; Henipavirus Infections/virology
  19. Yong MY, Lee SC, Ngui R, Lim YA, Phipps ME, Chang LY
    J Infect Dis, 2020 05 11;221(Suppl 4):S370-S374.
    PMID: 32392323 DOI: 10.1093/infdis/jiaa085
    Nipah virus (NiV) outbreak occurred in Malaysia in 1998. The natural host reservoir for NiV is Pteropus bats, which are commonly found throughout Malaysia. Humans become infected when NiV spills over from the reservoir species. In this study, NiV serosurveillance in Peninsular Malaysia, particularly among the indigenous population, was performed. The collected samples were tested for presence of NiV antibodies using a comparative indirect enzyme-linked immunosorbent assay based on the recombinant NiV nucleocapsid (rNiV-N) protein. We found that 10.73% of the participants recruited in this study had antibodies against rNiV-N, suggesting possible exposure to NiV.
    Matched MeSH terms: Henipavirus Infections/epidemiology*; Henipavirus Infections/virology*
  20. Bossart KN, Rockx B, Feldmann F, Brining D, Scott D, LaCasse R, et al.
    Sci Transl Med, 2012 Aug 08;4(146):146ra107.
    PMID: 22875827 DOI: 10.1126/scitranslmed.3004241
    In the 1990s, Hendra virus and Nipah virus (NiV), two closely related and previously unrecognized paramyxoviruses that cause severe disease and death in humans and a variety of animals, were discovered in Australia and Malaysia, respectively. Outbreaks of disease have occurred nearly every year since NiV was first discovered, with case fatality ranging from 10 to 100%. In the African green monkey (AGM), NiV causes a severe lethal respiratory and/or neurological disease that essentially mirrors fatal human disease. Thus, the AGM represents a reliable disease model for vaccine and therapeutic efficacy testing. We show that vaccination of AGMs with a recombinant subunit vaccine based on the henipavirus attachment G glycoprotein affords complete protection against subsequent NiV infection with no evidence of clinical disease, virus replication, or pathology observed in any challenged subjects. Success of the recombinant subunit vaccine in nonhuman primates provides crucial data in supporting its further preclinical development for potential human use.
    Matched MeSH terms: Henipavirus Infections/immunology; Henipavirus Infections/prevention & control
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