The Experts below are selected from a list of 2523 Experts worldwide ranked by ideXlab platform
Michael D. A. Lindsay - One of the best experts on this subject based on the ideXlab platform.
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the seroprevalence and factors associated with Ross River Virus infection in western grey kangaroos macropus fuliginosus in western australia
Vector-borne and Zoonotic Diseases, 2014Co-Authors: Abbey Potter, Cheryl A. Johansen, S A Reid, Stan Fenwick, Michael D. A. LindsayAbstract:A serosurvey was undertaken in 15 locations in the midwest to southwest of Western Australia (WA) to investigate the seroprevalence of Ross River Virus (RRV) neutralizing antibodies and factors associated with infection in western grey kangaroos (Macropus fuliginosus). The estimated seroprevalence in 2632 kangaroo samples, using a serum neutralization test, was 43.9% (95% CI 42.0, 45.8). Location was significantly associated with seroprevalence (p 0.05). The results of this study indicate that kangaroos in WA are regularly infected with RRV and may be involved in the maintenance and transmission of RRV.
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Ross River Virus risk associated with dispersal of aedes ochlerotatus camptorhynchus thomson from breeding habitat into surrounding residential areas muddy lakes western australia
American Journal of Tropical Medicine and Hygiene, 2014Co-Authors: Andrew Jardine, Peter J Neville, Colin Dent, Carla Webster, Michael D. A. LindsayAbstract:Rapid population growth in Western Australia has resulted in increased development of land for residential housing, and new developments are often proposed close to water because of intrinsic aesthetic values. However, this placement may place future residents at risk of mosquito-borne disease, of which Ross River Virus (RRV) disease is the most common in Australia. Mosquito dispersal data were combined with a spatial analysis of human RRV cases to show that mosquitoes dispersed readily from larval habitat into surrounding low- and high-density residential areas and that residents living within 2 km of mosquito breeding habitat had a significantly higher rate of RRV disease. This finding highlights the importance of planning authorities in state and local governments to consider the implications of mosquito-borne disease risks when assessing residential development applications.
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a comparison of the diseases caused by Ross River Virus and barmah forest Virus
The Medical Journal of Australia, 1998Co-Authors: James Flexman, Michael D. A. Lindsay, J R E Fraser, David Smith, J S Mackenzie, Simon P Bass, Linda Hueston, Anthony L CunninghamAbstract:Barmah Forest Virus (BFV) and Ross River Virus (RRV) are mosquito-borne Viruses with similar vectors and environmental requirements. They cause diseases characterised by arthralgia, arthritis and myalgia, often accompanied by fever and rash. Arthritis is more common and more prominent in RRV disease and rash is more common and florid with BFV infection, although the diseases cannot be reliably distinguished by their clinical symptoms. Diagnosis is based on serological tests and a definite diagnosis of recent infection requires the demonstration of rising titres of IgG. Arthralgia, myalgia and lethargy may continue for at least six months in up to half of patients with RRV, but in only about 10% of patients with BFV. Both diseases are managed symptomatically.
Alyssa T Pyke - One of the best experts on this subject based on the ideXlab platform.
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sucrose density gradient centrifugation and cRoss flow filtration methods for the production of arboVirus antigens inactivated by binary ethylenimine
BMC Microbiology, 2004Co-Authors: Alyssa T Pyke, Debra A Phillips, Teck F Chuan, Greg SmithAbstract:Sucrose density gradient centrifugation and cRoss-flow filtration methods have been developed and standardised for the safe and reproducible production of inactivated arboVirus antigens which are appropriate for use in diagnostic serological applications. To optimise the maximum titre of growth during the propagation of arboViruses, the multiplicity of infection and choice of cell line were investigated using stocks of Ross River Virus and Barmah Forest Virus grown in both mosquito and mammalian cell lines. To standardise and improve the efficacy of the inactivation of arboviral suspensions, stocks of Ross River Virus, Barmah Forest Virus, Japanese encephalitis Virus, Murray Valley encephalitis Virus and Alfuy Virus were chemically inactivated using binary ethylenimine at a final concentration of 3 mM. Aliquots were then taken at hourly intervals and crude inactivation rates were determined for each Virus using a plaque assay. To ensure complete inactivation, the same aliquots were each passaged 3 times in Aedes albopictus C6/36 cells and the presence of viral growth was detected using an immunofluorescent assay. For larger quantities of viral suspensions, centrifugation on an isopycnic sucrose density gradient or cRoss-flow filtration was used to produce concentrated, pure antigens or partially concentrated, semi-purified antigens respectively. The results of the propagation experiments suggested that the maximum viral titres obtained for both Ross River Virus and Barmah Forest Virus were affected by the incubation period and choice of cell line, rather than the use of different multiplicity of infection values. Results of the binary ethylenimine inactivation trial suggested that standardised periods of 5 or 8 hours would be suitable to ensure effective and complete inactivation for a number of different arboviral antigens. Two methods used to prepare inactivated arboVirus antigens have been standardised to minimise production failure and expenditure and to provide reagents that conform to the highest quality and safety requirements of a diagnostic serology laboratory. The antigens are suitable for use in either enzyme linked immunosorbent assays or haemagglutination inhibition assays and the optimised protocols can be directly applied to produce antigens from new or emerging arboviral pathogens.
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Sucrose density gradient centrifugation and cRoss-flow filtration methods for the production of arboVirus antigens inactivated by binary ethylenimine
BMC Microbiology, 2004Co-Authors: Alyssa T Pyke, Debra A Phillips, Teck F Chuan, Greg A SmithAbstract:Background Sucrose density gradient centrifugation and cRoss-flow filtration methods have been developed and standardised for the safe and reproducible production of inactivated arboVirus antigens which are appropriate for use in diagnostic serological applications. Methods To optimise the maximum titre of growth during the propagation of arboViruses, the multiplicity of infection and choice of cell line were investigated using stocks of Ross River Virus and Barmah Forest Virus grown in both mosquito and mammalian cell lines. To standardise and improve the efficacy of the inactivation of arboviral suspensions, stocks of Ross River Virus, Barmah Forest Virus, Japanese encephalitis Virus, Murray Valley encephalitis Virus and Alfuy Virus were chemically inactivated using binary ethylenimine at a final concentration of 3 mM. Aliquots were then taken at hourly intervals and crude inactivation rates were determined for each Virus using a plaque assay. To ensure complete inactivation, the same aliquots were each passaged 3 times in Aedes albopictus C6/36 cells and the presence of viral growth was detected using an immunofluorescent assay. For larger quantities of viral suspensions, centrifugation on an isopycnic sucrose density gradient or cRoss-flow filtration was used to produce concentrated, pure antigens or partially concentrated, semi-purified antigens respectively. Results The results of the propagation experiments suggested that the maximum viral titres obtained for both Ross River Virus and Barmah Forest Virus were affected by the incubation period and choice of cell line, rather than the use of different multiplicity of infection values. Results of the binary ethylenimine inactivation trial suggested that standardised periods of 5 or 8 hours would be suitable to ensure effective and complete inactivation for a number of different arboviral antigens. Conclusion Two methods used to prepare inactivated arboVirus antigens have been standardised to minimise production failure and expenditure and to provide reagents that conform to the highest quality and safety requirements of a diagnostic serology laboratory. The antigens are suitable for use in either enzyme linked immunosorbent assays or haemagglutination inhibition assays and the optimised protocols can be directly applied to produce antigens from new or emerging arboviral pathogens.
Timothy S. Baker - One of the best experts on this subject based on the ideXlab platform.
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aura Virus structure suggests that the t 4 organization is a fundamental property of viral structural proteins
Journal of Virology, 2002Co-Authors: Wei Zhang, James H. Strauss, Richard J. Kuhn, Bonnie R Fisher, Norman H Olson, Timothy S. BakerAbstract:Aura and Sindbis Viruses are closely related alphaViruses. Unlike other alphaViruses, Aura Virus efficiently encapsidates both genomic RNA (11.8 kb) and subgenomic RNA (4.2 kb) to form Virus particles. Previous studies on negatively stained Aura Virus particles predicted that there were two major size classes with potential T=3 and T=4 capsid structures. We have used cryoelectron microscopy and three-dimensional image reconstruction techniques to examine the native morphology of different classes of Aura Virus particles produced in BHK cells. Purified particles separated into two components in a sucrose gradient. Reconstructions of particles in the top and bottom components were computed to resolutions of 17 and 21 A, respectively, and compared with reconstructions of Sindbis Virus and Ross River Virus particles. Aura Virus particles of both top and bottom components have similar, T=4 structures that resemble those of other alphaViruses. The morphology of Aura Virus glycoprotein spikes closely resembles that of Sindbis Virus spikes and is detectably different from that of Ross River Virus spikes. Thus, some aspects of the surface structure of members of the Sindbis Virus lineage have been conserved, but other aspects have diverged from the Semliki Forest/Ross River Virus lineage.
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Aura Virus Structure Suggests that the T4 Organization Is a Fundamental Property of Viral Structural Proteins
2001Co-Authors: Richard J. Kuhn, Timothy S. BakerAbstract:Aura and Sindbis Viruses are closely related alphaViruses. Unlike other alphaViruses, Aura Virus efficiently encapsidates both genomic RNA (11.8 kb) and subgenomic RNA (4.2 kb) to form Virus particles. Previous studies on negatively stained Aura Virus particles predicted that there were two major size classes with potential T3 and T4 capsid structures. We have used cryoelectron microscopy and three-dimensional image reconstruction techniques to examine the native morphology of different classes of Aura Virus particles produced in BHK cells. Purified particles separated into two components in a sucrose gradient. Reconstruc-tions of particles in the top and bottom components were computed to resolutions of 17 and 21 Å, respectively, and compared with reconstructions of Sindbis Virus and Ross River Virus particles. Aura Virus particles of both top and bottom components have similar, T4 structures that resemble those of other alphaViruses. The morphology of Aura Virus glycoprotein spikes closely resembles that of Sindbis Virus spikes and is detectably different from that of Ross River Virus spikes. Thus, some aspects of the surface structure of members of the Sindbis Virus lineage have been conserved, but other aspects have diverged from the Semliki Forest/Ross River Virus lineage. AlphaVirus is a genus within the family Togaviridae that con-sists of about 26 members. AlphaViruses are enveloped, posi
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putative receptor binding sites on alphaViruses as visualized by cryoelectron microscopy
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Thomas J Smith, Richard J. Kuhn, R H Cheng, N H Olson, Peter E Peterson, Elaine Chase, Timothy S. BakerAbstract:Abstract The structures of Sindbis Virus and Ross River Virus complexed with Fab fragments from monoclonal antibodies have been determined from cryoelectron micrographs. Both antibodies chosen for this study bind to regions of the virions that have been implicated in cell-receptor recognition and recognize epitopes on the E2 glycoprotein. The two structures show that the Fab fragments bind to the outermost tip of the trimeric envelope spike protein. Hence, the same region of both the Sindbis Virus and Ross River Virus envelope spike is composed of E2 and is involved in recognition of the cellular receptor.
Cheryl A. Johansen - One of the best experts on this subject based on the ideXlab platform.
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Mosquito and Virus Surveillance as a Predictor of Human Ross River Virus Infection in South-West Western Australia: How Useful Is It?
The American journal of tropical medicine and hygiene, 2018Co-Authors: Liz J. Walker, Linda A. Selvey, Andrew Jardine, Cheryl A. JohansenAbstract:Mosquito and Virus surveillance systems are widely used in Western Australia (WA) to support public health efforts to reduce mosquito-borne disease. However, these programs are costly to maintain on a long-term basis. Therefore, we aimed to assess the validity of mosquito numbers and Ross River Virus (RRV) isolates from surveillance trap sites as predictors of human RRV cases in south-west WA between 2003 and 2014. Using negative binomial regression modeling, mosquito surveillance was found to be a useful tool for predicting human RRV cases. In eight of the nine traps, when adjusted for season, there was an increased risk of RRV cases associated with elevated mosquito numbers detected 1 month before the onset of human cases for at least one quartile compared with the reference group. The most predictive urban trap sites were located near saltmarsh mosquito habitat, bushland that could sustain macropods and densely populated residential suburbs. This convergence of environments could allow enzootic transmission of RRV to spillover and infect the human population. Close proximity of urban trap sites to each other suggested these sites could be reduced. Ross River Virus isolates were infrequent at some trap sites, so ceasing RRV isolation from mosquitoes at these sites or where isolates were not predictive of human cases could be considered. In future, trap sites could be reduced for routine surveillance, allowing other environments to be monitored to broaden the understanding of RRV ecology in the region. A more cost-effective and efficient surveillance program may result from these modifications.
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the seroprevalence and factors associated with Ross River Virus infection in western grey kangaroos macropus fuliginosus in western australia
Vector-borne and Zoonotic Diseases, 2014Co-Authors: Abbey Potter, Cheryl A. Johansen, S A Reid, Stan Fenwick, Michael D. A. LindsayAbstract:A serosurvey was undertaken in 15 locations in the midwest to southwest of Western Australia (WA) to investigate the seroprevalence of Ross River Virus (RRV) neutralizing antibodies and factors associated with infection in western grey kangaroos (Macropus fuliginosus). The estimated seroprevalence in 2632 kangaroo samples, using a serum neutralization test, was 43.9% (95% CI 42.0, 45.8). Location was significantly associated with seroprevalence (p 0.05). The results of this study indicate that kangaroos in WA are regularly infected with RRV and may be involved in the maintenance and transmission of RRV.
Suresh Mahalingam - One of the best experts on this subject based on the ideXlab platform.
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alphaVirus induced hyperactivation of pi3k akt directs pro viral metabolic changes
PLOS Pathogens, 2018Co-Authors: Michela Mazzon, Cecilia Castro, Bastian Thaa, Lifeng Liu, Margit Mutso, Xiang Liu, Suresh Mahalingam, Julian L Griffin, Mark MarshAbstract:Virus reprogramming of cellular metabolism is recognised as a critical determinant for viral growth. While most Viruses appear to activate central energy metabolism, different Viruses have been shown to rely on alternative mechanisms of metabolic activation. Whether related Viruses exploit conserved mechanisms and induce similar metabolic changes is currently unclear. In this work we investigate how two alphaViruses, Semliki Forest Virus and Ross River Virus, reprogram host metabolism and define the molecular mechanisms responsible. We demonstrate that in both cases the presence of a YXXM motif in the viral protein nsP3 is necessary for binding to the PI3K regulatory subunit p85 and for activating AKT. This leads to an increase in glucose metabolism towards the synthesis of fatty acids, although additional mechanisms of metabolic activation appear to be involved in Ross River Virus infection. Importantly, a Ross River Virus mutant that fails to activate AKT has an attenuated phenotype in vivo, suggesting that viral activation of PI3K/AKT contributes to virulence and disease.
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AlphaVirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes.
Public Library of Science (PLoS), 2018Co-Authors: Michela Mazzon, Cecilia Castro, Bastian Thaa, Lifeng Liu, Margit Mutso, Xiang Liu, Suresh Mahalingam, Julian L Griffin, Mark Marsh, Gerald M McinerneyAbstract:Virus reprogramming of cellular metabolism is recognised as a critical determinant for viral growth. While most Viruses appear to activate central energy metabolism, different Viruses have been shown to rely on alternative mechanisms of metabolic activation. Whether related Viruses exploit conserved mechanisms and induce similar metabolic changes is currently unclear. In this work we investigate how two alphaViruses, Semliki Forest Virus and Ross River Virus, reprogram host metabolism and define the molecular mechanisms responsible. We demonstrate that in both cases the presence of a YXXM motif in the viral protein nsP3 is necessary for binding to the PI3K regulatory subunit p85 and for activating AKT. This leads to an increase in glucose metabolism towards the synthesis of fatty acids, although additional mechanisms of metabolic activation appear to be involved in Ross River Virus infection. Importantly, a Ross River Virus mutant that fails to activate AKT has an attenuated phenotype in vivo, suggesting that viral activation of PI3K/AKT contributes to virulence and disease
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Decreased Virulence of Ross River Virus Harboring a Mutation in the First Cleavage Site of Nonstructural Polyprotein Is Caused by a Novel Mechanism Leading to Increased Production of Interferon-Inducing RNAs
American Society for Microbiology, 2018Co-Authors: Xiang Liu, Margit Mutso, Lara J Herrero, Age Utt, Anni Lepland, Adam Taylor, Jayaram Bettadapura, Penny A. Rudd, Andres Merits, Suresh MahalingamAbstract:Infection with Ross River Virus (RRV) causes debilitating polyarthritis and arthralgia in individuals. AlphaViruses are highly sensitive to type I interferon (IFN). Mutations at the conserved P3 position of the cleavage site between nonstructural protein 1 (nsP1) and nsP2 (1/2 site) modulate type I IFN induction for both RRV and Sindbis Virus (SINV). We constructed and characterized RRV-T48A534V, a mutant harboring an A534V substitution in the P1 position of the 1/2 site, and compared it to parental RRV-T48 and to RRV-T48A532V, SINVI538 and SINVT538 harboring different substitutions in the same region. A534V substitution resulted in impaired processing of RRV nonstructural polyprotein and in elevated production of replicase-generated pathogen-associated molecular pattern (PAMP) RNAs that induce expression of type I IFN. Both A532V and A534V substitutions affected synthesis of viral RNAs, though the effects of these closely located mutations were drastically different affecting mostly either the viral negative-strand RNA or genomic and subgenomic RNA levels, respectively. Synthesis of PAMP RNAs was also observed for SINV replicase, and it was increased by I538T substitution. In comparison to RRV-T48, RRV-T48A534V was attenuated in vitro and in vivo. Interestingly, when type I IFN-deficient cells and type I IFN receptor-deficient mice were infected with RRV-T48 or RRV-T48A534V, differences between these Viruses were no longer apparent. Compared to RRV-T48, RRV-T48A534V infection was associated with increased upregulation of type I IFN signaling proteins. We demonstrate novel mechanisms by which the A534V mutation affect viral nonstructural polyprotein processing that can impact PAMP RNA production, type I IFN induction/sensitivity, and disease.This study gives further insight into mechanisms of type I IFN modulation by the medically important alphaViruses Ross River Virus (RRV) and Sindbis Virus (SINV). By characterizing attenuated RRV mutants, the crucial role of amino acid residues in P1 and P3 positions (the first and third amino acid residues preceding the scissile bond) of the cleavage site between nsP1 and nsP2 regions was highlighted. The study uncovers a unique relationship between alphaVirus nonstructural polyprotein processing, RNA replication, production of different types of pathogen-associated molecular pattern (PAMP) RNAs, type I IFN induction, and disease pathogenesis. This study also highlights the importance of the host innate immune response in RRV infections. The viral determinants of type I IFN modulation provide potential drug targets for clinical treatment of alphaviral disease and offer new approaches for rational attenuation of alphaViruses for construction of vaccine candidates
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critical role for macrophage migration inhibitory factor mif in Ross River Virus induced arthritis and myositis
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Lara J Herrero, Michelle Nelson, Anon Srikiatkhachorn, Surapee Anantapreecha, Gunter Fingerlerowson, Richard Bucala, Eric F Morand, Leilani Llanes Santos, Suresh MahalingamAbstract:Arthrogenic alphaViruses, such as Ross River Virus (RRV), chikungunya, Sindbis, mayaro and o'nyong-nyong Viruses circulate endemically worldwide, frequently causing outbreaks of polyarthritis. The exact mechanisms of how alphaViruses induce polyarthritis remain ill defined, although macrophages are known to play a key role. Macrophage migration inhibitory factor (MIF) is an important cytokine involved in rheumatoid arthritis pathogenesis. Here, we characterize the role of MIF in alphaVirus-induced arthritides using a mouse model of RRV-induced arthritis, which has many characteristics of RRV disease in humans. RRV-infected WT mice developed severe disease associated with up-regulated MIF expression in serum and tissues, which corresponded to severe inflammation and tissue damage. MIF-deficient (MIF(-/-)) mice developed mild disease accompanied by a reduction in inflammatory infiltrates and muscle destruction in the tissues, despite having viral titers similar to WT mice. In addition, reconstitution of MIF into MIF(-/-) mice exacerbated RRV disease and treatment of mice with MIF antagonist ameliorated disease in WT mice. Collectively, these findings suggest that MIF plays a critical role in determining the clinical severity of alphaVirus-induced musculoskeletal disease and may provide a target for the development of antiviral pharmaceuticals. The prospect being that early treatment with MIF-blocking pharmaceuticals may curtail the debilitating arthritis associated with alphaviral infections.
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characterization of Ross River Virus tropism and Virus induced inflammation in a mouse model of viral arthritis and myositis
Journal of Virology, 2006Co-Authors: Thomas E Morrison, Suresh Mahalingam, Brett A Lidbury, Alan C Whitmore, Reed S Shabman, Mark T HeiseAbstract:Mosquito-borne alphaViruses are a significant cause of both encephalitic and arthritic disease in humans worldwide. In contrast to the encephalitic alphaViruses, the pathogenesis of alphaVirus-induced arthritic disease is not well understood. Utilizing a mouse model of Ross River Virus (RRV) disease, we found that the primary targets of RRV infection are bone, joint, and skeletal muscle tissues of the hind limbs in both outbred CD-1 mice and adult C57BL/6J mice. Moreover, histological analyses demonstrated that RRV infection resulted in severe inflammation of these tissues. Characterization of the inflammatory infiltrate within the skeletal muscle tissue identified inflammatory macrophages, NK cells, and CD4+ and CD8+ T lymphocytes. To determine the contribution of the adaptive immune system, the outcome of RRV-induced disease was examined in C57BL/6J RAG-1(-/-) mice, which lack functional T and B lymphocytes. RAG-1(-/-) and wild-type mice developed similar disease signs, infiltration of inflammatory macrophages and NK cells, and muscle pathology, suggesting that the adaptive immune response does not play a critical role in the development of disease. These results establish the mouse model of RRV disease as a useful system for the identification of viral and host factors that contribute to alphaVirus-induced arthritis and myositis.
