The Experts below are selected from a list of 9957 Experts worldwide ranked by ideXlab platform
Ashley L. St. John - One of the best experts on this subject based on the ideXlab platform.
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Japanese Encephalitis Virus neuropenetrance is driven by mast cell chymase
Nature Communications, 2019Co-Authors: Justin T. Hsieh, Abhay P. S. Rathore, Gayathri Soundarajan, Ashley L. St. JohnAbstract:Japanese Encephalitis Virus (JEV) is a leading cause of viral Encephalitis. However, the mechanisms of JEV penetration of the blood-brain-barrier (BBB) remain poorly understood. Mast cells (MCs) are granulated innate immune sentinels located perivascularly, including at the BBB. Here we show that JEV activates MCs, leading to the release of granule-associated proteases in vivo. MC-deficient mice display reduced BBB permeability during JEV infection compared to congenic wild-type (WT) mice, indicating that enhanced vascular leakage in the brain during JEV infection is MC-dependent. Moreover, MCs promoted increased JEV infection in the central nervous system (CNS), enhanced neurological deficits, and reduced survival in vivo. Mechanistically, chymase, a MC-specific protease, enhances JEV-induced breakdown of the BBB and cleavage of tight-junction proteins. Chymase inhibition reversed BBB leakage, reduced brain infection and neurological deficits during JEV infection, and prolonged survival, suggesting chymase is a novel therapeutic target to prevent JEV Encephalitis.
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Japanese Encephalitis Virus neuropenetrance is driven by mast cell chymase
Nature Publishing Group, 2019Co-Authors: Justin T. Hsieh, Abhay P. S. Rathore, Gayathri Soundarajan, Ashley L. St. JohnAbstract:How Japanese Encephalitis Virus (JEV) penetrates the blood-brain barrier (BBB) remains unclear. Here, using a genetic mouse model and a virulent JEV strain, the authors show that perivascular mast cells (MC) mediate JEV neuroinvasion and identify the MC-protease chymase as a potential therapeutic target
Fuquan Zhang - One of the best experts on this subject based on the ideXlab platform.
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expression of particulate form of Japanese Encephalitis Virus envelope protein in a stably transfected drosophila cell line
Virology Journal, 2007Co-Authors: Fuquan Zhang, Li Li Zhang, Marlen Aasachapman, Hongyi ZhangAbstract:Background Japanese Encephalitis Virus (JEV), a member of the family Flaviviridae, is an important mosquito-borne human pathogen. Its envelope glycoprotein (E) is the major determinant of the pathogenicity and host immune responses. In the present study, we explored the feasibility of producing recombinant JEV E protein in the Virus-free Drosophila expression system.
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amplification and cloning of the full length genome of Japanese Encephalitis Virus by a novel long rt pcr protocol in a cosmid vector
Journal of Virological Methods, 2001Co-Authors: Fuquan Zhang, Qingsheng Huang, Shaozhun Jiang, Hongyi ZhangAbstract:Abstract A novel and rapid full-length long RT-PCR technique was established to produce genome-length cDNA from Japanese Encephalitis Virus. In vitro positive strand RNA transcripts from the full-length RT-PCR amplicon including T7 promoter sequences at the 5′ end were proved to be infectious upon transfection. The full-length amplicon without the T7 promoter was cloned into a cosmid vector under the SP6 promoter. This stable clone, designated as pJEV-1, was characterised further and used as a genetic resource for generation of infectious RNA transcripts, gene manipulation and expression. The ‘run-off’ transcript from pJEV-1 with vector sequences at the either end of the insert was not infectious, but transcripts of the full-length PCR amplicon from pJEV-1 produced infectious Virus upon transfection. A transcript with an engineered Xho I site from two ligated PCR fragments amplified from pJEV-1 was also infectious. Furthermore, the coding region for premembrane and envelope proteins (preM-E) from pJEV-1 was subcloned and expressed in the Drosophila Expression System. The expressed protein showed correct molecular size and was immunoreactive with a Japanese Encephalitis Virus E protein-specific antibody. The derivation of genome-size cDNA from Japanese Encephalitis Virus and the stable clone will facilitate investigation of this Virus and elucidation of its pathogenesis at the molecular level.
Norbert Nowotny - One of the best experts on this subject based on the ideXlab platform.
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emergence of usutu Virus an african mosquito borne flaviVirus of the Japanese Encephalitis Virus group central europe
Emerging Infectious Diseases, 2002Co-Authors: Herbert Weissenböck, Barbara Rebelbauder, Helga Lussy, Jolanta Kolodziejek, Norbert NowotnyAbstract:During late summer 2001 in Austria, a series of deaths in several species of birds occurred, similar to the beginning of the West Nile Virus (WNV) epidemic in the United States. We necropsied the dead birds and examined them by various methods; pathologic and immunohistologic investigations suggested a WNV infection. Subsequently, the Virus was isolated, identified, partially sequenced, and subjected to phylogenetic analysis. The isolates exhibited 97% identity to Usutu Virus (USUV), a mosquito-borne FlaviVirus of the Japanese Encephalitis Virus group; USUV has never previously been observed outside Africa nor associated with fatal disease in animals or humans. If established in central Europe, this Virus may have considerable effects on avian populations; whether USUV has the potential to cause severe human disease is unknown.
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emergence of usutu Virus an african mosquito borne flaviVirus of the Japanese Encephalitis Virus group
2002Co-Authors: Herbert Weissenböck, Barbara Rebelbauder, Helga Lussy, Jolanta Kolodziejek, Norbert NowotnyAbstract:During late summer 2001 in Austria, a series of deaths in several species of birds occurred, similar to the beginning of the West Nile Virus (WNV) epidemic in the United States. We necropsied the dead birds and examined them by various methods; pathologic and immunohistologic investigations suggested a WNV infection. Subsequently, the Virus was isolated, identified, partially sequenced, and subjected to phylogenetic analysis. The isolates exhibited 97% identity to Usutu Virus (USUV), a mosquito-borne FlaviVirus of the Japanese Encephalitis Virus group; USUV has never previously been observed outside Africa nor associated with fatal disease in animals or humans. If established in central Europe, this Virus may have considerable effects on avian populations; whether USUV has the potential to cause severe human disease is unknown. sutu Virus (USUV) is a relatively unknown member of the mosquito-borne cluster within the FlaviVirus genus, closely related to important human pathogens such as Japanese Encephalitis Virus (JEV), Murray Valley Encephalitis Virus (MVEV), Dengue Virus (DENV), Yellow fever Virus (YFV), Saint Louis Encephalitis Virus (SLEV), and West Nile Virus (WNV) (1–3). Isolated for the first time from mosquitoes in South Africa in 1959 and named after a river in Swaziland (4), USUV was sporadically isolated from several mosquito and bird species over the next decades (5–7). Only two isolations have been reported from mammals, one from Praomys sp. (African soft-furred rats) and one from a man with fever and rash (5). The Virus has never been associated with severe or fatal diseases in animals or humans, and it has never before been observed outside tropical and subtropical Africa. From the beginning of August through mid-September
Hongyi Zhang - One of the best experts on this subject based on the ideXlab platform.
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expression of particulate form of Japanese Encephalitis Virus envelope protein in a stably transfected drosophila cell line
Virology Journal, 2007Co-Authors: Fuquan Zhang, Li Li Zhang, Marlen Aasachapman, Hongyi ZhangAbstract:Background Japanese Encephalitis Virus (JEV), a member of the family Flaviviridae, is an important mosquito-borne human pathogen. Its envelope glycoprotein (E) is the major determinant of the pathogenicity and host immune responses. In the present study, we explored the feasibility of producing recombinant JEV E protein in the Virus-free Drosophila expression system.
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amplification and cloning of the full length genome of Japanese Encephalitis Virus by a novel long rt pcr protocol in a cosmid vector
Journal of Virological Methods, 2001Co-Authors: Fuquan Zhang, Qingsheng Huang, Shaozhun Jiang, Hongyi ZhangAbstract:Abstract A novel and rapid full-length long RT-PCR technique was established to produce genome-length cDNA from Japanese Encephalitis Virus. In vitro positive strand RNA transcripts from the full-length RT-PCR amplicon including T7 promoter sequences at the 5′ end were proved to be infectious upon transfection. The full-length amplicon without the T7 promoter was cloned into a cosmid vector under the SP6 promoter. This stable clone, designated as pJEV-1, was characterised further and used as a genetic resource for generation of infectious RNA transcripts, gene manipulation and expression. The ‘run-off’ transcript from pJEV-1 with vector sequences at the either end of the insert was not infectious, but transcripts of the full-length PCR amplicon from pJEV-1 produced infectious Virus upon transfection. A transcript with an engineered Xho I site from two ligated PCR fragments amplified from pJEV-1 was also infectious. Furthermore, the coding region for premembrane and envelope proteins (preM-E) from pJEV-1 was subcloned and expressed in the Drosophila Expression System. The expressed protein showed correct molecular size and was immunoreactive with a Japanese Encephalitis Virus E protein-specific antibody. The derivation of genome-size cDNA from Japanese Encephalitis Virus and the stable clone will facilitate investigation of this Virus and elucidation of its pathogenesis at the molecular level.
Ching-len Liao - One of the best experts on this subject based on the ideXlab platform.
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human kinase phosphatase wide rnai screening identified checkpoint kinase 2 as a cellular factor facilitating Japanese Encephalitis Virus infection
Frontiers in Cellular and Infection Microbiology, 2018Co-Authors: Yi-lin Chan, Ching-len Liao, Yi-ling LinAbstract:Japanese Encephalitis Virus (JEV), a mosquito-borne flaviVirus, causes acute Encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, checkpoint kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated kinase in JEV-infected cells by using inhibitors reduced Virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.
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Japanese Encephalitis Virus replicon based vaccine expressing enteroVirus 71 epitope confers dual protection from lethal challenges
Journal of Biomedical Science, 2015Co-Authors: Yiting Huang, Jiateh Liao, Ching-len Liao, Yi-ling Lin, Lichen Yen, Yungkun ChangAbstract:Background To construct safer recombinant flaviVirus vaccine, we exploited Japanese Encephalitis Virus (JEV) replicon-based platform to generate single-round infectious particles (SRIPs) that expressed heterologous neutralizing epitope SP70 derived from enteroVirus-71 (EV71). Such pseudo-infectious Virus particles, named SRIP-SP70, although are not genuine viable Viruses, closely mimic live Virus infection to elicit immune responses within one round of viral life cycle.
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vimentin binding is critical for infection by the virulent strain of Japanese Encephalitis Virus
Cellular Microbiology, 2011Co-Authors: Jianjong Liang, Chiayi Yu, Ching-len LiaoAbstract:Summary Japanese Encephalitis Virus (JEV), a mosquito-borne flaviVirus, causes acute Encephalitis with high mortality in humans. We used a pair of virulent (RP-9) and attenuated (RP-2ms) variants of JEV to pull down the cell surface molecules bound with JEV particle; their identities were revealed by LC-MS/MS analysis. One major protein bound with RP-9 and weakly with RP-2ms was identified as the intermediate filament protein vimentin. Infection of RP-9 but not that of RP-2ms was blocked by anti-vimentin antibodies and by recombinant-expressed vimentin proteins. Knockdown of vimentin expression reduced the levels of viral binding and viral production of RP-9, but not that of RP-2ms. The different vimentin dependency for JEV infection could be attributed to the major structural envelope protein, as the recombinant RP-9 with an E-E138K mutation became resistant to anti-vimentin blockage. Furthermore, RP-2ms mainly depended on cell surface glycosaminoglycans for viral binding and it became vimentin-dependent only when binding to glycosaminoglycans was blocked. Thus, we suggest that vimentin contributes to virulent JEV infection and might be a new target to intervene in this deadly infection.
