87 research outputs found

    Venezuelan Equine Encephalitis Virus Transmission and Effect on Pathogenesis

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    Quantifying the dose of an arbovirus transmitted by mosquitoes is essential for designing pathogenesis studies simulating natural infection of vertebrates. Titration of saliva collected in vitro from infected mosquitoes may not accurately estimate titers transmitted during blood feeding, and infection by needle injection may affect vertebrate pathogenesis. We compared the amount of Venezuelan equine encephalitis virus collected from the saliva of Aedes taeniorhynchus to the amount injected into a mouse during blood feeding. Less virus was transmitted by mosquitoes in vivo (geometric mean 11 PFU) than was found for comparable times of salivation in vitro (mean saliva titer 74 PFU). We also observed slightly lower early and late viremia titers in mice that were needle injected with 8 PFU, which represents the low end of the in vivo transmission range. No differences in survival were detected, regardless of the dose or infection route

    Widespread Detection of Antibodies to Eastern Equine Encephalitis, West Nile, St. Louis Encephalitis, and Turlock Viruses in Various Species of Wild Birds from Across the United States

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    Wild birds serve as amplifying hosts for many arboviruses, and are thought to be responsible for introducing these viruses into new areas during migration as well as reintroducing them to places where winter temperatures disrupt mosquito-borne transmission. To learn more about four mosquito-borne arboviruses of concern to human or animal health, we tested sera from 997 wild birds of 54 species and 17 families across 44 states of the United States collected from January 1, 2013, through September 30, 2013. Samples were tested for antibody against eastern equine encephalitis, St. Louis encephalitis, West Nile, and Turlock viruses using plaque reduction neutralization tests with an endpoint of 80% or greater. Of the 333 (33.4%) birds that tested positive for antibody to at least one arbovirus, 29.7% were exposed to two or more arboviruses. Exposure to all four arboviruses was detected in Canada geese, double-crested cormorants, mallards, mute swans, laughing gulls, and American coots. Our results suggest that exposure to arboviruses is widespread in the United States across a diversity of wild bird species

    Equine Polyclonal Antibodies Prevent Acute Chikungunya Virus Infection in Mice

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    Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen that causes chikungunya disease (CHIK); the disease is characterized by fever, muscle ache, rash, and arthralgia. This arthralgia can be debilitating and long-lasting, seriously impacting quality of life for years. Currently, there is no specific therapy available for CHIKV infection. We have developed a despeciated equine polyclonal antibody (CHIKV-EIG) treatment against CHIKV and evaluated its protective efficacy in mouse models of CHIKV infection. In immunocompromised (IFNAR−/−) mice infected with CHIKV, daily treatment for five consecutive days with CHIKV-EIG administered at 100 mg/kg starting on the day of infection prevented mortality, reduced viremia, and improved clinical condition as measured by body weight loss. These beneficial effects were seen even when treatment was delayed to 1 day after infection. In immunocompetent mice, CHIKV-EIG treatment reduced virus induced arthritis (including footpad swelling), arthralgia-associated cytokines, viremia, and tissue virus loads in a dose-dependent fashion. Collectively, these results suggest that CHIKV-EIG is effective at preventing CHIK and could be a viable candidate for further development as a treatment for human disease

    Widespread Detection of Antibodies to Eastern Equine Encephalitis, West Nile, St. Louis Encephalitis, and Turlock Viruses in Various Species of Wild Birds from Across the United States

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    Wild birds serve as amplifying hosts for many arboviruses, and are thought to be responsible for introducing these viruses into new areas during migration as well as reintroducing them to places where winter temperatures disrupt mosquito-borne transmission. To learn more about four mosquito-borne arboviruses of concern to human or animal health, we tested sera from 997 wild birds of 54 species and 17 families across 44 states of the United States collected from January 1, 2013, through September 30, 2013. Samples were tested for antibody against eastern equine encephalitis, St. Louis encephalitis, West Nile, and Turlock viruses using plaque reduction neutralization tests with an endpoint of 80% or greater. Of the 333 (33.4%) birds that tested positive for antibody to at least one arbovirus, 29.7% were exposed to two or more arboviruses. Exposure to all four arboviruses was detected in Canada geese, double-crested cormorants, mallards, mute swans, laughing gulls, and American coots. Our results suggest that exposure to arboviruses is widespread in the United States across a diversity of wild bird species

    Serologic Evidence of Various Arboviruses Detected in White Tailed Deer (\u3ci\u3eOdocoileus virginianus\u3c/i\u3e) in the United States

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    White-tailed deer (Odocoileus virginianus) are an abundant mammal with a wide geographic distribution in the United States, which make them good sentinels for monitoring arboviral activity across the country. Exposure to various arboviruses has been detected in white-tailed deer, typically in conjunction with another diagnostic finding. To better assess the exposure of white-tailed deer to seven arboviruses, wetested 1,508 sera collected from 2010 to 2016 for antibodies to eastern equine encephalitis (2.5%), Powassan (4.2%), St. Louis encephalitis, (3.7%), West Nile (6.0%), Maguari (19.4%), La Crosse (30.3%), and bluetongue (7.8%) viruses. At least one arbovirus was detected in 51.3%, and exposure to more than one arbovirus was identified in 17.6% of the white-tailed deer sampled

    Novel Chikungunya Vaccine Candidate with an IRES-Based Attenuation and Host Range Alteration Mechanism

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    Chikungunya virus (CHIKV) is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES) from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus

    Study on the Failure Mechanism for Coal Roadway Stability in Jointed Rock Mass Due to the Excavation Unloading Effect

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    Aiming at the large deformation instability problem caused by the excavation unloading of a coal roadway in deep-buried slowly inclined jointed rock mass, the geomechanical parameters and deformation failure characteristics of an engineering geomechanical model were investigated. The in-situ stress state of the model was measured with the stress relief method. The geological and mechanical properties of roadway surrounding rock were described. The surrounding rock structure was revealed with the electron microscopy scanning method, micro-fractures and randomly distributed joints highly developed in roadway surrounding rock. Field investigation and monitoring indicated the cross-section of roadway surrounding rock shrank continuously and the deformation distribution was obviously asymmetric. Shotcrete spalling and cable broken failures frequently occurred in the middle and ride side of roof and right rib. Based on the geomechanical conditions of the coal roadway, a discrete element numerical model of coal roadway in gently inclined jointed rock mass was established. The parameters of rock mass in the numerical model were calibrated. The model ran in unsupported condition to restore the evolution process of stress, crack propagation and deformation in roadway surrounding rock due to gradual deviatoric stress release caused by excavation. On this basis, the space-time evolution characteristics and law of stress, crack propagation and deformation were obtained and then the asymmetric large fragmentation and dilatation deformation failure mechanism of roadway surrounding rock in deep-buried slowly inclined jointed rock mass was revealed. The failure reasons of the support structure were analyzed, and the relevant support principles were proposed. The research results can provide scientific references for the stability control of roadways excavated in jointed rock mass

    Dynamic Response Analysis of the Straddle-Type Monorail Bridge–Vehicle Coupling System

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    Abstract An analytical procedure of dynamic interaction analysis of the straddle monorail bridge–vehicle coupling system is proposed in this paper based on the finite element method and energy method. The calculation procedure is programmed with VB language for the solution of the governing motion equations of the straddle-type monorail bridge–vehicle coupling system. The effects of speed, three kinds of loads and different radius of curvature on dynamic responses of the monorail bridge–vehicle coupling system are analyzed. The simulation indicates that vertical vibration amplitude of the track beam decreases while the lateral amplitude increases with the increase in the radius of the curvature; the maximum value in lateral and vertical direction is 0.075 and 0.43 mm, respectively; and the maximum amplitude (lateral and vertical) and acceleration (lateral and vertical) are 0.69, 0.046 mm, 0.15 and 0.62 m/s2, respectively, at the speed of 80 km/h. The vibration amplitude (lateral and vertical) and vertical acceleration increase with the increasing load, and the maximum values are 0.041, 0.43 mm and 0.44 m/s2, respectively. The lateral acceleration is not easily affected by the load conditions
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