The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Hume Field - One of the best experts on this subject based on the ideXlab platform.
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synchronous shedding of multiple bat paramyxoViruses coincides with peak periods of Hendra Virus spillover
Emerging microbes & infections, 2019Co-Authors: Alison J. Peel, Daniel Edson, Michelle L. Baker, Victoria Boyd, Hume Field, Gary Crameri, John R Giles, Konstans Wells, Amy L BurroughsAbstract:Within host-parasite communities, viral co-circulation and co-infections of hosts are the norm, yet studies of significant emerging zoonoses tend to focus on a single parasite species within the host. Using a multiplexed paramyxoVirus bead-based PCR on urine samples from Australian flying foxes, we show that multi-viral shedding from flying fox populations is common. We detected up to nine bat paramyxoViruses shed synchronously. Multi-viral shedding infrequently coalesced into an extreme, brief and spatially restricted shedding pulse, coinciding with peak spillover of Hendra Virus, an emerging fatal zoonotic pathogen of high interest. Such extreme pulses of multi-viral shedding could easily be missed during routine surveillance yet have potentially serious consequences for spillover of novel pathogens to humans and domestic animal hosts. We also detected co-occurrence patterns suggestive of the presence of interactions among Viruses, such as facilitation and cross-immunity. We propose that multiple Viruses may be interacting, influencing the shedding and spillover of zoonotic pathogens. Understanding these interactions in the context of broader scale drivers, such as habitat loss, may help predict shedding pulses of Hendra Virus and other fatal zoonoses.
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australian horse owners and their biosecurity practices in the context of Hendra Virus
Preventive Veterinary Medicine, 2017Co-Authors: Anke K Wiethoelter, Nina Kung, Navneet K. Dhand, T Wright, Melanie R Taylor, Barbara Moloney, Kate Sawford, N Schembri, Hume FieldAbstract:In recent years, outbreaks of exotic as well as newly emerging infectious diseases have highlighted the importance of biosecurity for the Australian horse industry. As the first potentially fatal zoonosis transmissible from horses to humans in Australia, Hendra Virus has emphasised the need to incorporate sound hygiene and general biosecurity practices into day-to-day horse management. Recommended measures are widely publicised, but implementation is at the discretion of the individual owner. This cross-sectional study aimed to determine current levels of biosecurity of horse owners and to identify factors influencing the uptake of practices utilising data from an online survey. Level of biosecurity (low, medium, high), as determined by horse owners' responses to a set of questions on the frequency of various biosecurity practices performed around healthy (9 items) and sick horses (10 items), was used as a composite outcome variable in ordinal logistic regression analyses. The majority of horse owners surveyed were female (90%), from the states of Queensland (45%) or New South Wales (37%), and were involved in either mainly competitive/equestrian sports (37%) or recreational horse activities (35%). Seventy-five percent of owners indicated that they follow at least one-third of the recommended practices regularly when handling their horses, resulting in medium to high levels of biosecurity. Main factors associated with a higher level of biosecurity were high self-rated standard of biosecurity, access to personal protective equipment, absence of flying foxes in the local area, a good sense of control over Hendra Virus risk, likelihood of discussing a sick horse with a veterinarian and likelihood of suspecting Hendra Virus in a sick horse. Comparison of the outcome variable with the self-rated standard of biosecurity showed that over- as well as underestimation occurred. This highlights the need for continuous communication and education to enhance awareness and understanding of what biosecurity is and how it aligns with good horsemanship. Overall, strengthened biosecurity practices will help to improve animal as well as human health and increase preparedness for future disease outbreaks.
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Physiological stress and Hendra Virus in flying-foxes (Pteropus spp.), Australia.
PLOS ONE, 2017Co-Authors: Lee Mcmichael, Craig S Smith, Daniel Edson, Joanne Meers, Ina Smith, David G. Mayer, Steven R. Kopp, Hume FieldAbstract:Pteropid bats (flying-foxes) are the natural reservoir of Hendra Virus, an emergent paramyxoVirus responsible for fatal infection in horses and humans in Australia. Pteropus alecto (the Black flying-fox) and the paraphyletic P. conspicillatus (the Spectacled flying-fox) appear to be the primary reservoir hosts. Previous studies have suggested that physiological and ecological factors may underpin infection dynamics in flying-foxes, and subsequent spillover to horses and in turn humans. We sought to examine temporal trends in urinary cortisol concentration in wild Australian flying-fox populations, to elucidate the putative relationship between Hendra Virus infection and physiological stress. Pooled and individual urine samples were non-invasively collected from under roosting flying-foxes at two latitudinally disparate regions in the eastern Australian state of Queensland. Hendra Virus detection, and (in individual urine samples) sex and species determination were PCR-based. Urinary cortisol measurement used a validated enzyme immunoassay. We found no direct correlation between increased urinary cortisol and Hendra Virus excretion, but our findings do suggest a biologically plausible association between low winter temperatures and elevated cortisol levels in P. alecto in the lower latitude Southeast Queensland roosts. We hypothesize an indirect association between low winter temperatures and increased Hendra Virus infection and excretion, mediated by the physiological cost of thermoregulation. Our findings and our approach are directly relevant to elaboration of the disease ecology of Nipah Virus and other emerging henipaViruses in bats. More broadly, they inform investigation of emerging disease infection dynamics across the wildlife/livestock/human interface.
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we ve learned to live with it a qualitative study of australian horse owners attitudes perceptions and practices in response to Hendra Virus
Preventive Veterinary Medicine, 2017Co-Authors: Anke K Wiethoelter, Nina Kung, Hume Field, Navneet K. Dhand, T Wright, Melanie R Taylor, Barbara Moloney, Kate Sawford, N Schembri, Jennyann L M L ToribioAbstract:Hendra Virus causes sporadic zoonotic disease in Australia following spill over from flying foxes to horses and from horses to people. Prevention and risk mitigation strategies such as vaccination of horses or biosecurity and property management measures are widely publicised, but hinge on initiative and action taken by horse owners as they mediate management, care and treatment of their animals. Hence, underlying beliefs, values and attitudes of horse owners influence their uptake of recommended risk mitigation measures. We used a qualitative approach to investigate attitudes, perceptions and self-reported practices of horse owners in response to Hendra Virus to gain a deeper understanding of their decision-making around prevention measures. Data presented here derive from a series of in-depth interviews with 27 horse owners from Hendra Virus ‘hot spot’ areas in New South Wales and Queensland. Interviews explored previous experience, perceptions and resulting behaviour as well as communication around Hendra Virus. All interviews were recorded, transcribed verbatim and analysed in NVivo using thematic analysis. Analysis revealed four major themes: perception of Hendra Virus as a risk and factors influencing this perception, Hendra Virus risk mitigation strategies implemented by horse owners, perceived motivators and barriers of these strategies, and interaction of perceived risk, motivators and barriers in the decision-making process. Although Hendra Virus disease was perceived as a serious threat to the health of horses and humans, individual risk perception diverged among horse owners. Perceived severity, likelihood and unpredictability as well as awareness and knowledge of Hendra Virus, trust in information obtained and information pathways, demographic characteristics and personal experience were the main factors influencing Hendra Virus risk perceptions. Other key determinants of horse owners’ decision-making process were attitudes towards Hendra Virus risk mitigation measures as well as perceived motivators and barriers thereof. Horse owners’ awareness of the necessity to consider individual Hendra Virus risk and adequate risk management strategies was described as a learning process, which changed over time. However, different perceptions of risk, barriers and motivators in combination with a weighing up of advantages and disadvantages resulted in different behaviours. These findings demonstrate the multifactorial determinants of cognitive mediating processes and facilitate a better understanding of horse owners’ perspectives on preventive horse health measures. Furthermore, they provide valuable feedback to industry and government stakeholders on how to improve effective risk communication and encourage uptake of recommended risk mitigation measures.
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PHYSIOLOGIC BIOMARKERS AND Hendra Virus INFECTION IN AUSTRALIAN BLACK FLYING FOXES (PTEROPUS ALECTO).
Journal of Wildlife Diseases, 2016Co-Authors: Lee Mcmichael, Daniel Edson, Joanne Meers, David G. Mayer, Alice Broos, Steven R. Kopp, Hume FieldAbstract:Abstract Bats of the genus Pteropus (Pteropodidae), colloquially known as flying foxes, are recognized as the natural reservoir of Hendra Virus, a zoonotic paramyxoVirus responsible for mortality in horses and humans. Some previous studies have suggested that physiologic and ecologic factors promote Hendra Virus infection in flying foxes, and by extension, spillover to horses and humans. However, the impact of Hendra Virus infection on relevant physiologic biomarkers in flying foxes has not been measured. Over 12 mo in eastern Australia, we captured and sampled 446 individual black flying foxes (Pteropus alecto), a putative primary reservoir host species, and measured a suite of hematologic, plasma biochemistry, and urinary biomarkers. All mean hematologic and biochemical values in both Hendra Virus–positive and Virus–negative cohorts were within the published reference ranges for black flying foxes. We found no association between Hendra Virus infection (as indicated by PCR detection of Hendra Virus RNA)...
Linfa Wang - One of the best experts on this subject based on the ideXlab platform.
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circulating microrna profiles of Hendra Virus infection in horses
Scientific Reports, 2017Co-Authors: Christopher Cowled, Linfa Wang, Deborah Middleton, Christina L Rootes, Chwan Hong Foo, Celine Deffrasnes, David T Williams, Andrew G D Bean, Cameron R. StewartAbstract:Hendra Virus (HeV) is an emerging zoonotic pathogen harbored by Australian mainland flying foxes. HeV infection can cause lethal disease in humans and horses, and to date all cases of human HeV disease have resulted from contact with infected horses. Currently, diagnosis of acute HeV infections in horses relies on the productive phase of infection when Virus shedding may occur. An assay that identifies infected horses during the preclinical phase of infection would reduce the risk of zoonotic viral transmission during management of HeV outbreaks. Having previously shown that the host microRNA (miR)-146a is upregulated in the blood of HeV-infected horses days prior to the detection of viremia, we have profiled miRNAs at the transcriptome-wide level to comprehensively assess differences between infected and uninfected horses. Next-generation sequencing and the miRDeep2 algorithm identified 742 mature miRNA transcripts corresponding to 593 miRNAs in whole blood of six horses (three HeV-infected, three uninfected). Thirty seven miRNAs were differentially expressed in infected horses, two of which were validated by qRT-PCR. This study describes a methodology for the transcriptome-wide profiling of miRNAs in whole blood and supports the notion that measuring host miRNA expression levels may aid infectious disease diagnosis in the future.
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Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats
2016Co-Authors: Jonathan H. Epstein, Michelle L. Baker, Carlos Zambrana-torrelio, Deborah Middleton, Jennifer Barr Edward A. Dubovi, Allyson Walsh, Katey Pelican, Mark D. Fielder, Angela J. Davies, Linfa WangAbstract:Old World frugivorous bats have been identified as natural hosts for emerging zoonotic Viruses of significant public health concern, including henipaViruses (Nipah and Hendra Virus), Ebola Virus, and Marburg Virus. Epidemiological studies of these Viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper Virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra Virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaViruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanu
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potent inhibition of Hendra Virus infection via rna interference and poly i c immune activation
PLOS ONE, 2013Co-Authors: Jana Mccaskill, Linfa Wang, Glenn A. Marsh, Paul Monaghan, Timothy J Doran, Nigel A J McmillanAbstract:Hendra Virus (HeV) is a highly pathogenic zoonotic paramyxoVirus that causes fatal disease in a wide range of species, including humans. HeV was first described in Australia in 1994, and has continued to re-emerge with increasing frequency. HeV is of significant concern to human health due to its high mortality rate, increasing emergence, absence of vaccines and limited post exposure therapies. Here we investigate the use of RNA interference (RNAi) based therapeutics targeting HeV in conjunction with the TLR3 agonist Poly I:C and show that they are potent inhibitors of HeV infection in vitro. We found that short interfering RNAs (siRNAs) targeting the abundantly expressed N, P and M genes of HeV caused over 95% reduction of HeV Virus titre, protein and mRNA. Furthermore, we found that the combination of HeV targeting siRNA and Poly I:C had an additive effect in suppressing HeV infection. Our results demonstrate for the first time that RNAi and type I interferon stimulation are effective inhibitors of HeV replication in vitro and may provide an effective therapy for this highly lethal, zoonotic pathogen.
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rapid detection of Hendra Virus using magnetic particles and quantum dots
Advanced Healthcare Materials, 2012Co-Authors: Fabio Lisi, Linfa Wang, Gary Crameri, Paolo Falcaro, Dario Buso, Anita J Hill, Jennifer A Barr, Tichlam Nguyen, Paul MulvaneyAbstract:A proof-of-concept for the development of a fast and portable Hendra Virus biosensor is presented. Hendra Virus, a deadly emerging pathogen in Australia, can be co-localized, concentrated and revealed using simultaneously magnetic and luminescent functional particles. This method should be applicable for the early detection of any other Virus by targeting the specific Virus with the corresponding antibody.
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a new model for Hendra Virus encephalitis in the mouse
PLOS ONE, 2012Co-Authors: Johanna Dups, Deborah Middleton, Glenn A. Marsh, Rachel Robinson, Manabu Yamada, Paul Monaghan, Fenella Long, Linfa WangAbstract:Hendra Virus (HeV) infection in humans is characterized by an influenza like illness, which may progress to pneumonia or encephalitis and lead to death. The pathogenesis of HeV infection is poorly understood, and the lack of a mouse model has limited the opportunities for pathogenetic research. In this project we reassessed the role of mice as an animal model for HeV infection and found that mice are susceptible to HeV infection after intranasal exposure, with aged mice reliably developing encephalitic disease. We propose an anterograde route of neuroinvasion to the brain, possibly along olfactory nerves. This is supported by evidence for the development of encephalitis in the absence of viremia and the sequential distribution of viral antigen along pathways of olfaction in the brain of intranasally challenged animals. In our studies mice developed transient lower respiratory tract infection without progressing to viremia and systemic vasculitis that is common to other animal models. These studies report a new animal model of HeV encephalitis that will allow more detailed studies of the neuropathogenesis of HeV infection, particularly the mode of viral spread and possible sequestration within the central nervous system; investigation of mechanisms that moderate the development of viremia and systemic disease; and inform the development of improved treatment options for human patients.
Yanru Feng - One of the best experts on this subject based on the ideXlab platform.
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an antibody against the f glycoprotein inhibits nipah and Hendra Virus infections
Nature Structural & Molecular Biology, 2019Co-Authors: Ha V Dang, Yanru Feng, Barry Rockx, Yeepeng Chan, Lianying Yan, Youngjun Park, Joost Snijder, Sofia Cheliout Da SilvaAbstract:Nipah Virus (NiV) and Hendra Virus (HeV) are zoonotic henipaViruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.
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a recombinant Hendra Virus g glycoprotein subunit vaccine protects nonhuman primates against Hendra Virus challenge
Journal of Virology, 2014Co-Authors: Chad E Mire, Christopher C Broder, Katharine N. Bossart, Yanru Feng, Joan B Geisbert, Yeepeng Chan, Krystle N Agans, Karla A Fenton, Lianying Yan, Thomas W GeisbertAbstract:Hendra Virus (HeV) is a zoonotic emerging Virus belonging to the family Paramyxoviridae. HeV causes severe and often fatal respiratory and/or neurologic disease in both animals and humans. Currently, there are no licensed vaccines or antiviral drugs approved for human use. A number of animal models have been developed for studying HeV infection, with the African green monkey (AGM) appearing to most faithfully reproduce the human disease. Here, we assessed the utility of a newly developed recombinant subunit vaccine based on the HeV attachment (G) glycoprotein in the AGM model. Four AGMs were vaccinated with two doses of the HeV vaccine (sGHeV) containing Alhydrogel, four AGMs received the sGHeV with Alhydrogel and CpG, and four control animals did not receive the sGHeV vaccine. Animals were challenged with a high dose of infectious HeV 21 days after the boost vaccination. None of the eight specifically vaccinated animals showed any evidence of clinical illness and survived the challenge. All four controls became severely ill with symptoms consistent with HeV infection, and three of the four animals succumbed 8 days after exposure. Success of the recombinant subunit vaccine in AGMs provides pivotal data in supporting its further preclinical development for potential human use. IMPORTANCE A Hendra Virus attachment (G) glycoprotein subunit vaccine was tested in nonhuman primates to assess its ability to protect them from a lethal infection with Hendra Virus. It was found that all vaccinated African green monkeys were completely protected against subsequent Hendra Virus infection and disease. The success of this new subunit vaccine in nonhuman primates provides critical data in support of its further development for future human use.
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Hendra Virus vaccine a one health approach to protecting horse human and environmental health
Emerging Infectious Diseases, 2014Co-Authors: Deborah Middleton, Jessica Haining, Yanru Feng, Jackie Pallister, Reuben Klein, Rachel Arkinstall, Leah Frazer, Jinan Huang, Nigel Edwards, Mark WareingAbstract:In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra Virus (HeV), a zoonotic paramyxoVirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease.
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a Hendra Virus g glycoprotein subunit vaccine protects african green monkeys from nipah Virus challenge
Science Translational Medicine, 2012Co-Authors: Katharine N. Bossart, Yanru Feng, Barry Rockx, Friederike Feldmann, Doug Brining, Dana Scott, Rachel Lacasse, Joan B Geisbert, Yeepeng ChanAbstract: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.
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a recombinant Hendra Virus g glycoprotein based subunit vaccine protects ferrets from lethal Hendra Virus challenge
Vaccine, 2011Co-Authors: Jackie Pallister, Linfa Wang, Deborah Middleton, Jessica Haining, Rachel Robinson, John R White, Reuben Klein, Manabu Yamada, Jean Payne, Yanru FengAbstract:Abstract The henipaViruses, Hendra Virus (HeV) and Nipah Virus (NiV), are two deadly zoonotic Viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents Virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID 50 of HeV. In addition, and of considerable importance, no evidence of Virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible.
Deborah Middleton - One of the best experts on this subject based on the ideXlab platform.
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circulating microrna profiles of Hendra Virus infection in horses
Scientific Reports, 2017Co-Authors: Christopher Cowled, Linfa Wang, Deborah Middleton, Christina L Rootes, Chwan Hong Foo, Celine Deffrasnes, David T Williams, Andrew G D Bean, Cameron R. StewartAbstract:Hendra Virus (HeV) is an emerging zoonotic pathogen harbored by Australian mainland flying foxes. HeV infection can cause lethal disease in humans and horses, and to date all cases of human HeV disease have resulted from contact with infected horses. Currently, diagnosis of acute HeV infections in horses relies on the productive phase of infection when Virus shedding may occur. An assay that identifies infected horses during the preclinical phase of infection would reduce the risk of zoonotic viral transmission during management of HeV outbreaks. Having previously shown that the host microRNA (miR)-146a is upregulated in the blood of HeV-infected horses days prior to the detection of viremia, we have profiled miRNAs at the transcriptome-wide level to comprehensively assess differences between infected and uninfected horses. Next-generation sequencing and the miRDeep2 algorithm identified 742 mature miRNA transcripts corresponding to 593 miRNAs in whole blood of six horses (three HeV-infected, three uninfected). Thirty seven miRNAs were differentially expressed in infected horses, two of which were validated by qRT-PCR. This study describes a methodology for the transcriptome-wide profiling of miRNAs in whole blood and supports the notion that measuring host miRNA expression levels may aid infectious disease diagnosis in the future.
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Duration of Maternal Antibodies against Canine Distemper Virus and Hendra Virus in Pteropid Bats
2016Co-Authors: Jonathan H. Epstein, Michelle L. Baker, Carlos Zambrana-torrelio, Deborah Middleton, Jennifer Barr Edward A. Dubovi, Allyson Walsh, Katey Pelican, Mark D. Fielder, Angela J. Davies, Linfa WangAbstract:Old World frugivorous bats have been identified as natural hosts for emerging zoonotic Viruses of significant public health concern, including henipaViruses (Nipah and Hendra Virus), Ebola Virus, and Marburg Virus. Epidemiological studies of these Viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper Virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra Virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaViruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanu
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Hendra Virus infection in dog australia 2013
Emerging Infectious Diseases, 2015Co-Authors: Peter D Kirkland, T Wright, Melinda Gabor, Ian Poe, Kristie Neale, Kim Chaffey, Deborah S Finlaison, Paul Hick, A J Read, Deborah MiddletonAbstract:Hendra Virus occasionally causes severe disease in horses and humans. In Australia in 2013, infection was detected in a dog that had been in contact with an infected horse. Abnormalities and viral RNA were found in the dog’s kidney, brain, lymph nodes, spleen, and liver. Dogs should be kept away from infected horses.
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Hendra Virus vaccine a one health approach to protecting horse human and environmental health
Emerging Infectious Diseases, 2014Co-Authors: Deborah Middleton, Jessica Haining, Yanru Feng, Jackie Pallister, Reuben Klein, Rachel Arkinstall, Leah Frazer, Jinan Huang, Nigel Edwards, Mark WareingAbstract:In recent years, the emergence of several highly pathogenic zoonotic diseases in humans has led to a renewed emphasis on the interconnectedness of human, animal, and environmental health, otherwise known as One Health. For example, Hendra Virus (HeV), a zoonotic paramyxoVirus, was discovered in 1994, and since then, infections have occurred in 7 humans, each of whom had a strong epidemiologic link to similarly affected horses. As a consequence of these outbreaks, eradication of bat populations was discussed, despite their crucial environmental roles in pollination and reduction of the insect population. We describe the development and evaluation of a vaccine for horses with the potential for breaking the chain of HeV transmission from bats to horses to humans, thereby protecting horse, human, and environmental health. The HeV vaccine for horses is a key example of a One Health approach to the control of human disease.
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duration of maternal antibodies against canine distemper Virus and Hendra Virus in pteropid bats
PLOS ONE, 2013Co-Authors: Michelle L. Baker, Victoria Boyd, Jonathan H. Epstein, Deborah Middleton, Jennifer A Barr, Carlos Zambranatorrelio, Edward J Dubovi, Brian Pope, Shawn ToddAbstract:Old World frugivorous bats have been identified as natural hosts for emerging zoonotic Viruses of significant public health concern, including henipaViruses (Nipah and Hendra Virus), Ebola Virus, and Marburg Virus. Epidemiological studies of these Viruses in bats often utilize serology to describe viral dynamics, with particular attention paid to juveniles, whose birth increases the overall susceptibility of the population to a viral outbreak once maternal immunity wanes. However, little is understood about bat immunology, including the duration of maternal antibodies in neonates. Understanding duration of maternally derived immunity is critical for characterizing viral dynamics in bat populations, which may help assess the risk of spillover to humans. We conducted two separate studies of pregnant Pteropus bat species and their offspring to measure the half-life and duration of antibodies to 1) canine distemper Virus antigen in vaccinated captive Pteropus hypomelanus; and 2) Hendra Virus in wild-caught, naturally infected Pteropus alecto. Both of these pteropid bat species are known reservoirs for henipaViruses. We found that in both species, antibodies were transferred from dam to pup. In P. hypomelanus pups, titers against CDV waned over a mean period of 228.6 days (95% CI: 185.4-271.8) and had a mean terminal phase half-life of 96.0 days (CI 95%: 30.7-299.7). In P. alecto pups, antibodies waned over 255.13 days (95% CI: 221.0-289.3) and had a mean terminal phase half-life of 52.24 days (CI 95%: 33.76-80.83). Each species showed a duration of transferred maternal immunity of between 7.5 and 8.5 months, which was longer than has been previously estimated. These data will allow for more accurate interpretation of age-related HenipaVirus serological data collected from wild pteropid bats.
Christopher C Broder - One of the best experts on this subject based on the ideXlab platform.
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a single dose investigational subunit vaccine for human use against nipah Virus and Hendra Virus
NPJ Vaccines, 2021Co-Authors: Thomas W Geisbert, Joan B Geisbert, Krystle N Agans, Karla A Fenton, Kathryn Bobb, Viktoriya Borisevich, Robert W Cross, Abhishek N Prasad, Timothy R Fouts, Christopher C BroderAbstract:Nipah and Hendra Viruses are highly pathogenic bat-borne paramyxoViruses recently included in the WHO Blueprint priority diseases list. A fully registered horse anti-Hendra Virus subunit vaccine has been in use in Australia since 2012. Based on the same immunogen, the Hendra Virus attachment glycoprotein ectodomain, a subunit vaccine formulation for use in people is now in a Phase I clinical trial. We report that a single dose vaccination regimen of this human vaccine formulation protects against otherwise lethal challenges of either Hendra or Nipah Virus in a nonhuman primate model. The protection against the Nipah Bangladesh strain begins as soon as 7 days post immunization with low dose of 0.1 mg protein subunit. Our data suggest this human vaccine could be utilized as efficient emergency vaccine to disrupt potential spreading of Nipah disease in an outbreak setting.
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Hendra Virus and nipah Virus animal vaccines
Vaccine, 2016Co-Authors: Christopher C Broder, Dawn L Weir, Peter A ReidAbstract: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.
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a recombinant Hendra Virus g glycoprotein subunit vaccine protects nonhuman primates against Hendra Virus challenge
Journal of Virology, 2014Co-Authors: Chad E Mire, Christopher C Broder, Katharine N. Bossart, Yanru Feng, Joan B Geisbert, Yeepeng Chan, Krystle N Agans, Karla A Fenton, Lianying Yan, Thomas W GeisbertAbstract:Hendra Virus (HeV) is a zoonotic emerging Virus belonging to the family Paramyxoviridae. HeV causes severe and often fatal respiratory and/or neurologic disease in both animals and humans. Currently, there are no licensed vaccines or antiviral drugs approved for human use. A number of animal models have been developed for studying HeV infection, with the African green monkey (AGM) appearing to most faithfully reproduce the human disease. Here, we assessed the utility of a newly developed recombinant subunit vaccine based on the HeV attachment (G) glycoprotein in the AGM model. Four AGMs were vaccinated with two doses of the HeV vaccine (sGHeV) containing Alhydrogel, four AGMs received the sGHeV with Alhydrogel and CpG, and four control animals did not receive the sGHeV vaccine. Animals were challenged with a high dose of infectious HeV 21 days after the boost vaccination. None of the eight specifically vaccinated animals showed any evidence of clinical illness and survived the challenge. All four controls became severely ill with symptoms consistent with HeV infection, and three of the four animals succumbed 8 days after exposure. Success of the recombinant subunit vaccine in AGMs provides pivotal data in supporting its further preclinical development for potential human use. IMPORTANCE A Hendra Virus attachment (G) glycoprotein subunit vaccine was tested in nonhuman primates to assess its ability to protect them from a lethal infection with Hendra Virus. It was found that all vaccinated African green monkeys were completely protected against subsequent Hendra Virus infection and disease. The success of this new subunit vaccine in nonhuman primates provides critical data in support of its further development for future human use.
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developments towards effective treatments for nipah and Hendra Virus infection
Expert Review of Anti-infective Therapy, 2006Co-Authors: Katharine N. Bossart, Christopher C BroderAbstract: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 research conducted on the henipaViruses over the past several years has focused on Virus entry, including the attachment of Virus to the host cell, the identification of the Virus receptor and the membrane fusion process between the viral and host cell membranes. These findings have led to the development of possible vaccine candidates, as well as potential antiviral therapeutics. The common link among all of the possible antiviral agents discussed here, which have also been developed and tested, is that they target very early stages of the infection process. The establishment and validation of suitable animal models of HenipaVirus infection and pathogenesis are also discussed as they will be crucial in the assessment of the effectiveness of any treatments for Hendra and Nipah Virus infection.
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functional expression and membrane fusion tropism of the envelope glycoproteins of Hendra Virus
Virology, 2001Co-Authors: Katharine N. Bossart, Linfa Wang, Bryan T Eaton, Christopher C BroderAbstract:Hendra Virus (HeV) is an emerging paramyxoVirus first isolated from cases of severe respiratory disease that fatally affected both horses and humans. Understanding the mechanisms of host cell infection and cross-species transmission is an important step in addressing the risk posed by such emerging pathogens. We have initiated studies to characterize the biological properties of the HeV envelope glycoproteins. Recombinant vaccinia Viruses encoding the HeV F and G open reading frames were generated and glycoprotein expression was verified by metabolic labeling and detection using specific antisera. Glycoprotein function and cellular tropism were examined with a quantitative assay for HeV-mediated membrane fusion. Fusion specificity was verified through specific inhibition by anti-HeV antiserum and a peptide corresponding to one of the alpha-helical heptad repeats of F. HeV requires both F and G to mediate fusion. Permissive target cells have been identified, including cell lines derived from cat, bat, horse, human, monkey, mouse, and rabbit. Fusion negative cell types have also been identified. Protease treatments of the target cells abolished fusion activity, suggesting that the Virus is employing a cell-surface protein as its receptor.
