The Experts below are selected from a list of 8097 Experts worldwide ranked by ideXlab platform
Kristen A. Bernard - One of the best experts on this subject based on the ideXlab platform.
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Tissue Tropism and neuroinvasion of West Nile virus do not differ for two mouse strains with different survival rates
Virology, 2007Co-Authors: Ashley N. Brown, Kim A. Kent, Corey J. Bennett, Kristen A. BernardAbstract:West Nile virus (WNV) is a mosquito-borne flavivirus that infects the central nervous system of humans and other animals. In this study, we found that C3H/HeN (C3H) mice exhibited a higher morbidity and mortality than C57BL/6 (B6) mice. We compared Tissue Tropism, viral replication and kinetics for C3H and B6 mice during acute viral infection. WNV was detected in multiple Tissues, including novel sites such as the skin, duodenum and pancreas, but the Tropism was identical for the two strains. Additionally, viral load and kinetics of spread did not differ substantially between strains. Neuroinvasion occurred in both strains by day 3 post-inoculation with early detection in the olfactory bulbs and spinal cord, suggesting that WNV neuroinvades at specific sites. Furthermore, neuroinvasion and viral load in the CNS did not predict disease outcome. Our data suggest that the disparities in morbidity and mortality between C3H and B6 mice are not due to differences in Tropism, viral load or kinetics during acute WNV infection.
Paul E Love - One of the best experts on this subject based on the ideXlab platform.
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retinoic acid determines the precise Tissue Tropism of inflammatory th17 cells in the intestine
Journal of Immunology, 2010Co-Authors: C R Wang, Seung G Kang, Harm Hogenesch, Paul E LoveAbstract:Th17 cells are major effector T cells in the intestine, but the regulation of their Tissue Tropism within the gut is poorly understood. We investigated the roles of vitamin A and retinoic acid in generation of inflammatory Th17 cells with distinct Tissue Tropisms within the intestine. We found that Th17 cells with distinct Tissue Tropisms and pathogenic activities are generated depending on the available concentration of retinoic acid (RA). In contrast to the widespread perception that RA would suppress the generation of Th17 cells, we provide evidence that RA is actually required for generation of Th17 cells with specific Tissue Tropisms within the gut. Th17 cells induced at suboptimal serum concentrations of RA migrated and induced moderate inflammation mainly in the large intestine, whereas the Th17 cells induced with optimal levels of exogenous RA (∼10 nM) migrated to the small intestine and induced more severe inflammation. The Th17 cells, induced in the presence or absence of RA, differentially expressed the trafficking receptors CCR9 and α4β7. CCR9 is required for Th17 cell migration to the small intestine, whereas α4β7 is required for the migration of Th17 cells throughout the whole intestine. Our results identified RA as a major signal that regulates the generation of gut Th17 cells with distinct capacities in migration and inflammatory activities. The results indicate also that specific gut Tropism of Th17 cells is determined by the combination of trafficking receptors regulated by the RA signal.
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Retinoic Acid Determines the Precise Tissue Tropism of Inflammatory Th17 Cells in the Intestine
Journal of immunology (Baltimore Md. : 1950), 2010Co-Authors: Chuanwu Wang, Harm Hogenesch, Seung G Kang, Paul E Love, Chang H. KimAbstract:Th17 cells are major effector T cells in the intestine, but the regulation of their Tissue Tropism within the gut is poorly understood. We investigated the roles of vitamin A and retinoic acid in generation of inflammatory Th17 cells with distinct Tissue Tropisms within the intestine. We found that Th17 cells with distinct Tissue Tropisms and pathogenic activities are generated depending on the available concentration of retinoic acid (RA). In contrast to the widespread perception that RA would suppress the generation of Th17 cells, we provide evidence that RA is actually required for generation of Th17 cells with specific Tissue Tropisms within the gut. Th17 cells induced at suboptimal serum concentrations of RA migrated and induced moderate inflammation mainly in the large intestine, whereas the Th17 cells induced with optimal levels of exogenous RA (approximately 10 nM) migrated to the small intestine and induced more severe inflammation. The Th17 cells, induced in the presence or absence of RA, differentially expressed the trafficking receptors CCR9 and alpha4beta7. CCR9 is required for Th17 cell migration to the small intestine, whereas alpha4beta7 is required for the migration of Th17 cells throughout the whole intestine. Our results identified RA as a major signal that regulates the generation of gut Th17 cells with distinct capacities in migration and inflammatory activities. The results indicate also that specific gut Tropism of Th17 cells is determined by the combination of trafficking receptors regulated by the RA signal.
Robert E. Johnston - One of the best experts on this subject based on the ideXlab platform.
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Alpha/beta interferon protects adult mice from fatal Sindbis virus infection and is an important determinant of cell and Tissue Tropism.
Journal of virology, 2000Co-Authors: Kate D. Ryman, William B. Klimstra, Khuong B. Nguyen, Christine A. Biron, Robert E. JohnstonAbstract:Infection of adult 129 Sv/Ev mice with consensus Sindbis virus strain TR339 is subclinical due to an inherent restriction in early virus replication and viremic dissemination. By comparing the pathogenesis of TR339 in 129 Sv/Ev mice and alpha/beta interferon receptor null (IFN-α/βR−/−) mice, we have assessed the contribution of IFN-α/β in restricting virus replication and spread and in determining cell and Tissue Tropism. In adult 129 Sv/Ev mice, subcutaneous inoculation with 100 PFU of TR339 led to extremely low-level virus replication and viremia, with clearance under way by 96 h postinoculation (p.i.). In striking contrast, adult IFN-α/βR−/− mice inoculated subcutaneously with 100 PFU of TR339 succumbed to the infection within 84 h. By 24 h p.i. a high-titer serum viremia had seeded infectious virus systemically, coincident with the systemic induction of the proinflammatory cytokines interleukin-12 (IL-12) p40, IFN-γ, tumor necrosis factor alpha, and IL-6. Replicating virus was located in macrophage-dendritic cell (DC)-like cells at 24 h p.i. in the draining lymph node and in the splenic marginal zone. By 72 h p.i. virus replication was widespread in macrophage-DC-like cells in the spleen, liver, lung, thymus, and kidney and in fibroblast-connective Tissue and periosteum, with sporadic neuroinvasion. IFN-α/β-mediated restriction of TR339 infection was mimicked in vitro in peritoneal exudate cells from 129 Sv/Ev versus IFN-α/βR−/− mice. Thus, IFN-α/β protects the normal adult host from viral infection by rapidly conferring an antiviral state on otherwise permissive cell types, both locally and systemically. Ablation of the IFN-α/β system alters the apparent cell and Tissue Tropism of the virus and renders macrophage-DC-lineage cells permissive to infection.
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alpha beta interferon protects adult mice from fatal sindbis virus infection and is an important determinant of cell and Tissue Tropism
Journal of Virology, 2000Co-Authors: Kate D. Ryman, William B. Klimstra, Khuong B. Nguyen, Christine A. Biron, Robert E. JohnstonAbstract:Infection of adult 129 Sv/Ev mice with consensus Sindbis virus strain TR339 is subclinical due to an inherent restriction in early virus replication and viremic dissemination. By comparing the pathogenesis of TR339 in 129 Sv/Ev mice and alpha/beta interferon receptor null (IFN-α/βR−/−) mice, we have assessed the contribution of IFN-α/β in restricting virus replication and spread and in determining cell and Tissue Tropism. In adult 129 Sv/Ev mice, subcutaneous inoculation with 100 PFU of TR339 led to extremely low-level virus replication and viremia, with clearance under way by 96 h postinoculation (p.i.). In striking contrast, adult IFN-α/βR−/− mice inoculated subcutaneously with 100 PFU of TR339 succumbed to the infection within 84 h. By 24 h p.i. a high-titer serum viremia had seeded infectious virus systemically, coincident with the systemic induction of the proinflammatory cytokines interleukin-12 (IL-12) p40, IFN-γ, tumor necrosis factor alpha, and IL-6. Replicating virus was located in macrophage-dendritic cell (DC)-like cells at 24 h p.i. in the draining lymph node and in the splenic marginal zone. By 72 h p.i. virus replication was widespread in macrophage-DC-like cells in the spleen, liver, lung, thymus, and kidney and in fibroblast-connective Tissue and periosteum, with sporadic neuroinvasion. IFN-α/β-mediated restriction of TR339 infection was mimicked in vitro in peritoneal exudate cells from 129 Sv/Ev versus IFN-α/βR−/− mice. Thus, IFN-α/β protects the normal adult host from viral infection by rapidly conferring an antiviral state on otherwise permissive cell types, both locally and systemically. Ablation of the IFN-α/β system alters the apparent cell and Tissue Tropism of the virus and renders macrophage-DC-lineage cells permissive to infection.
Debra E Bessen - One of the best experts on this subject based on the ideXlab platform.
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Variation in Streptococcus pyogenes NAD+ Glycohydrolase Is Associated with Tissue Tropism
Journal of bacteriology, 2010Co-Authors: David J. Riddle, Debra E Bessen, Michael G. CaparonAbstract:Streptococcus pyogenes is an important pathogen that causes a variety of diseases. The most common infections involve the throat (pharyngitis) or skin (impetigo); however, the factors that determine Tissue Tropism and severity are incompletely understood. The S. pyogenes NAD+ glycohydrolase (SPN) is a virulence factor that has been implicated in contributing to the pathogenesis of severe infections. However, the role of SPN in determining the bacterium's Tissue Tropism has not been evaluated. In this report, we examine the sequences of spn and its endogenous inhibitor ifs from a worldwide collection of S. pyogenes strains. Analysis of average pairwise nucleotide diversity, average number of nucleotide differences, and ratio of nonsynonymous to synonymous substitutions revealed significant diversity in spn and ifs. Application of established models of molecular evolution shows that SPN is evolving under positive selection and diverging into NAD+ glycohydrolase (NADase)-active and -inactive subtypes. Additionally, the NADase-inactive SPN subtypes maintain the characteristics of a functional gene while ifs becomes a pseudogene. Thus, NADase-inactive SPN continues to evolve under functional constraint. Furthermore, NADase activity did not correlate with invasive disease in our collection but was associated with Tissue Tropism. The ability to cause infection at both the pharynx and the skin (“generalist” strains) is correlated with NADase-active SPN, while the preference for causing infection at either the throat or the skin (“specialist” strains) is associated with NADase-inactive SPN. These findings suggest that SPN has a NADase-independent function and prompt a reevaluation of the role of SPN in streptococcal pathogenesis.
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role for a secreted cysteine proteinase in the establishment of host Tissue Tropism by group a streptococci
Molecular Microbiology, 2000Co-Authors: Mikael Svensson, Arne Olsen, Dominick A Scaramuzzino, Ulf Sjobring, Charlotte Frank, Debra E BessenAbstract:Primary infection of the human host by group A streptococci (GAS) most often involves either the epidermis of the skin or the oropharyngeal mucosa. A humanized in vivo model for impetigo was used to investigate the basis for host Tissue Tropism among GAS. Disruption of the speB gene (encoding for a secreted cysteine proteinase) led to a loss of virulence for two impetigo-derived strains (M-types 33 and 53), as evidenced by a diminution in Tissue damage and a lack of reproductive growth. The level of cysteine proteinase activity in overnight cultures was associated with the extent of gross pathological changes induced by strains displaying varied degrees of virulence in the impetigo model. Moreover, high levels of secreted cysteine proteinase activity correlated with a genetic marker for preferred Tissue site of infection at the skin (emm pattern D). The addition of exogenous SpeB to a speB mutant (emm pattern D) or to an avirulent throat-like strain (emm pattern A) led to increased bacterial reproduction at the skin. The data provide both experimental and epidemiological evidence for a critical role of a secreted bacterial protease in promoting host Tissue-specific infection.
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genetic linkage of exotoxin alleles and emm gene markers for Tissue Tropism in group a streptococci
The Journal of Infectious Diseases, 1999Co-Authors: Debra E Bessen, Marc W Izzo, Therese R Fiorentino, Romeo M Caringal, Susan K Hollingshead, Bernard BeallAbstract:In group A streptococci, genetic markers for principal Tissue reservoir are located within emm genes, which encode surface proteins that have a role in virulence. A worldwide collection of 160 isolates was evaluated for two traits: chromosomal emm gene markers for Tissue Tropism (designated patterns A-E), and bacteriophage-associated genes (speA and speC) encoding pyrogenic exotoxins. The speA and speC alleles of organisms harboring the emm marker for a pharyngeal reservoir (pattern A-C) differ from spe alleles that predominate in organisms with the emm marker for impetigo (pattern D). However, organisms that display the emm marker for both Tissue sites (pattern E) are not intermediate for the distribution of either speA or speC alleles, but instead resemble pattern A-C isolates for speA and pattern D strains for speC. Statistically significant nonrandom associations between exotoxin alleles and emm patterns were observed but cannot be readily explained by niche separation alone.
Michael S. Diamond - One of the best experts on this subject based on the ideXlab platform.
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Zika Virus Pathogenesis and Tissue Tropism
Cell host & microbe, 2017Co-Authors: Jonathan J. Miner, Michael S. DiamondAbstract:Although Zika virus (ZIKV) was isolated approximately 70 years ago, few experimental studies had been published prior to 2016. The recent spread of ZIKV to countries in the Western Hemisphere is associated with reports of microcephaly, congenital malformations, and Guillain-Barre syndrome. This has resulted in ZIKV being declared a public health emergency and has greatly accelerated the pace of ZIKV research and discovery. Within a short time period, useful mouse and non-human primate disease models have been established, and pre-clinical evaluation of therapeutics and vaccines has begun. Unexpectedly, ZIKV exhibits a broad Tropism and persistence in body Tissues and fluids, which contributes to the clinical manifestations and epidemiology that have been observed during the current epidemic. In this Review, we highlight recent advances in our understanding of ZIKV pathogenesis, Tissue Tropism, and the resulting pathology and discuss areas for future investigation.