Browsing by Subject "vector"
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Item Pathogenesis and transmission of Venezuelan equine encephalitis virus(2006-04-03) Darci Renee Smith; Scott C. Weaver; Robert B. Tesh; Lynn Soong; Judith F. Aronson; Ilya V. Frolov; George V. LudwigVenezuelan equine encephalitis virus (VEEV) is an emerging arboviral pathogen that affects the Americas. Outbreaks can involve hundreds- of- thousands of equines and humans, spread over large geographic regions, and can last several years. The principal vector in most major coastal outbreaks is the mosquito Aedes taeniorhynchus. This species is more susceptible to most epidemic than to enzootic strains, and the adaptation of VEEV to this vector may be an important determinant of epidemic transmission. However, studies on the infection, dissemination, and transmission of VEEV regarding this important vector are lacking. \r\nThe major determinant of Ae. taeniorhynchus infection with VEEV is the E2 envelope glycoprotein, which interacts with cellular receptors. I therefore hypothesized that differential interactions of VEEV with receptors on midgut epithelial cells determine the ability of a representative epidemic versus a representative enzootic strain to infect this mosquito. In support of this hypothesis, I found that significantly more epidemic VEEV bound to and infected mosquito midguts compared to the enzootic strain. The dissemination from the midgut of an epidemic VEEV strain was compared to that of an enzootic strain. Following initial infection, the epidemic strain was pantropic in tissues of the mosquito, including the salivary glands, whereas the enzootic strain did not infect the midgut efficiently and replicated only in muscles and nervous tissue upon dissemination. \r\nFollowing the infection of the mosquito salivary glands with an epidemic strain, the amount of VEEV transmitted was estimated. I hypothesized that the method of mosquito infection and saliva collection significantly affects estimates of the amount of virus transmitted and that differing infection routes affect the viremia and mortality of mice. Both the mosquito species and infection route used affected the amount of virus detected in the saliva. The amount of VEEV transmitted in vivo by mosquitoes during blood feeding was significantly less than in vitro transmission estimates and mosquito transmission had little or no effect on murine viremia or mortality compared to needle inoculations. These results have important implications for evaluating the vector competence of Ae. taeniorhynchus and other VEEV vectors, for designing pathogenesis experiments, and for modeling transmission in nature.\r\nItem The role of mosquito saliva on host immune response and pathogenesis of West Nile virus\r\n(2006-11-03) Bradley S Schneider; Stephen Higgs; Lynn Soong; Judith Aronson; Eric Smith; Donald ChampagneWest Nile virus is a positive sense single-stranded RNA virus in the family Flaviviridae that emerged globally following the appearance of a more neurotropic subtype. Recently outbreaks of WNV disease have occurred in the Middle East, Europe, Africa, South America, and North America. Vertebrates typically become infected when an infectious mosquito pierces the host epidermis to take a blood meal, depositing virus principally in the extravascular tissue. Accumulating evidence has demonstrated that the mosquito saliva, which carries WNV into the vertebrate, is not simply a transport medium, but can have a profound effect on vertebrate immunity, pathogen transmission efficiency, pathogenesis, and disease course. In the past most small animal models of arbovirus disease have used needle-inoculation, but recent evidence suggests that because of the potential effects of mosquito saliva on the immune system, it is important to re-evaluate the pathogenesis of these infections in the presence of mosquito saliva. A central question of this dissertation project was to determine if mosquito feeding or mosquito saliva could impact WNV disease. To evaluate the potential for mosquito saliva to alter WNV infection, the mouse model of disease employed in this dissertation revealed a potentiation of WNV disease when mosquitoes were allowed to feed at the virus inoculation site immediately before injection of WNV. Further, with higher titer inoculations of WNV subsequent to the feeding of mosquitoes more progressive infection, higher viremia, and accelerated neuroinvasion developed than the mice inoculated with an equivalent titer of WNV alone. To determine the mechanism of this potentiation, the in vivo expression of key TH1, TH2, inflammatory, and antiviral cytokines was quantified during peripheral arbovirus infection in the presence or absence of mosquito saliva. Data clearly showed that during early arbovirus infection mosquito salivary proteins down-modulates specific antiviral cytokines while enhancing production of TH2 and immunosuppressive cytokines. To understand the source of these shifts in immune signalling, the in vitro response of DCs and macrophages was investigated. Following exposure to Ae. aegypti SGE, APCs recently exposed to arbovirus displayed reductions in IFN-? and iNOS expression and transient amplification of IL-10 mRNA levels. Macrophages appeared to be more susceptible to the modulating effects of mosquito saliva than DCs. The influence of mosquito saliva on immune cell migration patterns both into the dermal site of WNV inoculation and the draining lymph node was also evaluated. The principal observation from this study was that the inclusion of mosquito saliva/feeding at the inoculation site of WNV leads to a suppression of lymphocytes, particularly CD4+ T cells, and a corresponding increase in DCs. Finally, although mosquito exposure and sensitization to it is widespread, the effect of prior exposure to mosquitoes on subsequent arbovirus infection had up until this point been unexplored. Accordingly, the potential for an immune response directed against mosquito salivary proteins to have a protective or confounding effect on naturally transmitted WNV infection was investigated by comparing early WNV pathogenesis in mosquito naïve and sensitized populations of mice. Previous exposure to Ae. aegypti feeding results in significantly higher mortality rates associated with elevation of inflammation, APC recruitment, and IL-4 expression concurrent with a decrease in lymphocytes mainly the CD4+ subtype. Mosquito sensitization-mediated amplification of WNV disease is facilitated by the humoral response to mosquito salivary proteins. This dissertation confirms that by ignoring the possible effects of the vector we may misinterpret the early immune response to arboviruses and also possibly aspects of the overall pathogenesis of arboviral infections. The information from the present study provides insight into early host responses to arbovirus infection, and suggests further determinants of WNV virulence.Item The Robust Classification of Hyperspectral Images Using Adaptive Wavelet Kernel Support Vector Data Description(2012-07-16) Kollegala, RevathiDetection of targets in hyperspectral images is a specific case of one-class classification. It is particularly relevant in the area of remote sensing and has received considerable interest in the past few years. The thesis proposes the use of wavelet functions as kernels with Support Vector Data Description for target detection in hyperspectral images. Specifically, it proposes the Adaptive Wavelet Kernel Support Vector Data Description (AWK-SVDD) that learns the optimal wavelet function to be used given the target signature. The performance and computational requirements of AWK-SVDD is compared with that of existing methods and other wavelet functions. An introduction to target detection and target detection in the context of hyperspectral images is given. This thesis also includes an overview of the thesis and lists the contributions of the thesis. A brief mathematical background into one-class classification in reference to target detection is included. Also described are the existing methods and introduces essential concepts relevant to the proposed approach. The use of wavelet functions as kernels with Support Vector Data Description, the conditions for use of wavelet functions and the use of two functions in order to form the kernel are checked and analyzed. The proposed approach, AWKSVDD, is mathematically described. The details of the implementation and the results when applied to the Urban dataset of hyperspectral images with a random target signature are given. The results confirm the better performance of AWK-SVDD compared to conventional kernels, wavelet kernels and the two-function Morlet-Radial Basis Function kernel. The problems faced with convergence during the Support Vector Data Description optimization are discussed. The thesis concludes with the suggestions for future work.