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Michael Roggendorf - One of the best experts on this subject based on the ideXlab platform.
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Immunization with recombinant woodchuck hepatitis Virus Nucleocapsid antigen or hepatitis B Virus Nucleocapsid antigen protects woodchucks from woodchuck hepatitis Virus infection.
Vaccine, 2002Co-Authors: Florian Schodel, Darrell L Peterson, Georg Neckermann, Steve Fuller, Hans Will, Klaus Fuchs, Michael RoggendorfAbstract:Woodchucks were immunized with recombinant woodchuck hepatitis Virus (WHV) Nucleocapsid antigen (WHcAg) or hepatitis B Virus (HBV) Nucleocapsid antigen (HBcAg) and challenged with 106 WHV ID50. Six out of six woodchucks immunized with WHcAg and four out of six immunized with HBcAg were protected from WHV infection. Woodchucks immunized with WHcAg or HBcAg developed high serum antibody titres against WHcAg or HBcAg. Antibodies against WHc and HBc displayed little cross-reactivity (
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immunization with recombinant woodchuck hepatitis Virus Nucleocapsid antigen or hepatitis b Virus Nucleocapsid antigen protects woodchucks from woodchuck hepatitis Virus infection
Vaccine, 1993Co-Authors: Florian Schodel, Darrell L Peterson, Georg Neckermann, Steve Fuller, Hans Will, Klaus Fuchs, Michael RoggendorfAbstract:Woodchucks were immunized with recombinant woodchuck hepatitis Virus (WHV) Nucleocapsid antigen (WHcAg) or hepatitis B Virus (HBV) Nucleocapsid antigen (HBcAg) and challenged with 106 WHV ID50. Six out of six woodchucks immunized with WHcAg and four out of six immunized with HBcAg were protected from WHV infection. Woodchucks immunized with WHcAg or HBcAg developed high serum antibody titres against WHcAg or HBcAg. Antibodies against WHc and HBc displayed little cross-reactivity (<1%). This confirms and extends previous reports of protection against homologous challenge after immunization with HBcAg/WHcAg which are both internal viral antigens. As the dominant B-cell epitope(s) on particulate WHcAg and HBcAg appear not to be conserved it also demonstrates that antibodies against HBcAg/WHcAg are not important for this protection. Woodchucks immunized with WHcAg/HBcAg reacted with a fast serum antibody response against viral envelope proteins upon challenge with WHV, indicative of functional intrastructural/intermolecular T-cell help as one potential mechanism of protection after immunization with an internal viral antigen.
Deborah L Galson - One of the best experts on this subject based on the ideXlab platform.
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TBK1 mediates critical effects of measles Virus Nucleocapsid protein (MVNP) on pagetic osteoclast formation.
Journal of Bone and Mineral Research, 2013Co-Authors: Benedicte Sammut, Noriyoshi Kurihara, Feng-ming Wang, Jolene J Windle, G. David Roodman, Deborah L GalsonAbstract:Paget's disease of bone (PDB) is characterized by abnormal osteoclasts with unique characteristics that include increased sensitivity of osteoclast progenitors to 1,25(OH)2D3, receptor activator of NF-κB ligand (RANKL), and TNF-α; increased osteoclast numbers; and increased expression of IL-6 and several transcription factors. We recently reported that measles Virus Nucleocapsid protein (MVNP) plays a key role in the development of these abnormal osteoclasts. MVNP can induce the pagetic osteoclast phenotype in vitro and in vivo in TRAP-MVNP transgenic mice. However, the molecular mechanisms by which MVNP generates pagetic osteoclasts have not been determined. TANK-binding kinase 1 (TBK1) and IκB kinase-ϵ (IKKϵ) are IKK family members that complex with MVNP and activate both IRF3 and NF-κB pathways. MVNP increases the amount of TBK1 protein in bone marrow monocytes (BMM). Interestingly, we found that RANKL increased TBK1 and IKKϵ early in osteoclast differentiation, suggesting a possible role in normal osteoclastogenesis. However, only TBK1 is further increased in osteoclasts formed by TRAP-MVNP BMM owing to increased TBK1 protein stability. TBK1 overexpression induced IL6 promoter reporter activity, and elevated endogenous IL6 mRNA and p65 NF-κB, TAF12, and ATF7 proteins in several cell lines. Overexpression of TBK1 was insufficient to induce pagetic osteoclasts from WT BMM but synergized with MVNP to increase pagetic osteoclast formation from TRAP-MVNP BMM. BX795 inhibition of TBK1 impaired MVNP-induced IL-6 expression in both NIH3T3 cells and BMM, and shRNA knockdown of Tbk1 in NIH3T3 cells impaired IL-6 secretion induced by MVNP and decreased TAF12 and ATF7, factors involved in 1,25(OH)2D3 hypersensitivity of pagetic osteoclasts. Similarly, Tbk1 knockdown in BMM from TRAP-MVNP and WT mice specifically impaired development of the MVNP-induced osteoclast pagetic phenotype. These results demonstrate that TBK1 plays a critical role in mediating the effects of MVNP on osteoclast differentiation and on the expression of IL-6, a key contributor to the pagetic osteoclast phenotype. © 2014 American Society for Bone and Mineral Research.
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TBK1 mediates critical effects of measles Virus Nucleocapsid protein (MVNP) on pagetic osteoclast formation.
Journal of Bone and Mineral Research, 2013Co-Authors: Quanhong Sun, Noriyoshi Kurihara, Benedicte Sammut, Feng-ming Wang, Jolene J Windle, G. David Roodman, Deborah L GalsonAbstract:Paget's disease of bone (PDB) is characterized by abnormal osteoclasts with unique characteristics that include increased sensitivity of osteoclast progenitors to 1,25(OH)2 D3 , receptor activator of NF-κB ligand (RANKL), and TNF-α; increased osteoclast numbers; and increased expression of IL-6 and several transcription factors. We recently reported that measles Virus Nucleocapsid protein (MVNP) plays a key role in the development of these abnormal osteoclasts. MVNP can induce the pagetic osteoclast phenotype in vitro and in vivo in TRAP-MVNP transgenic mice. However, the molecular mechanisms by which MVNP generates pagetic osteoclasts have not been determined. TANK-binding kinase 1 (TBK1) and IκB kinase-ϵ (IKKϵ) are IKK family members that complex with MVNP and activate both IRF3 and NF-κB pathways. MVNP increases the amount of TBK1 protein in bone marrow monocytes (BMM). Interestingly, we found that RANKL increased TBK1 and IKKϵ early in osteoclast differentiation, suggesting a possible role in normal osteoclastogenesis. However, only TBK1 is further increased in osteoclasts formed by TRAP-MVNP BMM owing to increased TBK1 protein stability. TBK1 overexpression induced IL6 promoter reporter activity, and elevated endogenous IL6 mRNA and p65 NF-κB, TAF12, and ATF7 proteins in several cell lines. Overexpression of TBK1 was insufficient to induce pagetic osteoclasts from WT BMM but synergized with MVNP to increase pagetic osteoclast formation from TRAP-MVNP BMM. BX795 inhibition of TBK1 impaired MVNP-induced IL-6 expression in both NIH3T3 cells and BMM, and shRNA knockdown of Tbk1 in NIH3T3 cells impaired IL-6 secretion induced by MVNP and decreased TAF12 and ATF7, factors involved in 1,25(OH)2 D3 hypersensitivity of pagetic osteoclasts. Similarly, Tbk1 knockdown in BMM from TRAP-MVNP and WT mice specifically impaired development of the MVNP-induced osteoclast pagetic phenotype. These results demonstrate that TBK1 plays a critical role in mediating the effects of MVNP on osteoclast differentiation and on the expression of IL-6, a key contributor to the pagetic osteoclast phenotype.
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measles Virus Nucleocapsid protein a key contributor to paget s disease increases il 6 expression via down regulation of foxo3 sirt1 signaling
Bone, 2013Co-Authors: Benedicte Sammut, Feng-ming Wang, Jolene J Windle, Aliye Sarmasik, Yuko Hiruma, Quanhong Sun, David G Roodman, Deborah L GalsonAbstract:Measles Virus plays an important role as an environmental factor in the pathogenesis of Paget's disease (PD). Previous studies have shown that IL-6 is increased in the bone marrow of Paget's patients and that measles Virus Nucleocapsid protein (MVNP) induces IL-6 secretion by pagetic osteoclasts. Further, IL-6 plays a critical role in the development of pagetic osteoclasts and bone lesions induced by PD, but the mechanisms regulating IL-6 production by MVNP remain unclear. Our current studies revealed that MVNP expression in osteoclast precursors down-regulated Sirt1 mRNA and protein, a negative regulator of NF-κB activity, which is a key factor for IL-6 expression. MVNP expression in NIH3T3 cells also elevated Il-6 transcription and impaired the expression of Sirt1 mRNA both under basal conditions and upon activation of the Sirt1 upstream regulator FoxO3 by LY294002 (a PI3K/AKT inhibitor). Luciferase activity assays showed that constitutively active FoxO3 abolished the repressive effect of MVNP on reporters driven by either FoxO3 response elements or the Sirt1 promoter. Further, protein stability assays revealed that FoxO3 was degraded more rapidly in MVNP-expressing cells than in control cells following the addition of cycloheximide. Similarly, co-transfection of MVNP and FoxO3 into HEK293 cells demonstrated that MVNP decreased the protein levels of over-expressed FoxO3 in a dose-dependent manner. Treatment with the proteasome inhibitor, MG132, blocked the MVNP-triggered decrease of FoxO3, and the treatment with the serine/threonine phosphatase inhibitor, calyculin A, revealed that MVNP increased phosphorylation of FoxO3. Further, over-expression of Sirt1 or treatment with the Sirt1 activator resveratrol blocked the increase in Il-6 transcription by MVNP. Finally, resveratrol reduced the numbers of TRAP positive multi-nuclear cells in bone marrow cultures from TRAP-MVNP transgenic mice to wild type levels. These results indicate that MVNP decreases FoxO3/Sirt1 signaling to enhance the levels of IL-6, which in part mediate MVNP's contribution to the development of Paget's disease.
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Measles Virus Nucleocapsid protein, a key contributor to Paget's disease, increases IL-6 expression via down-regulation of FoxO3/Sirt1 signaling
Bone, 2013Co-Authors: Feng-ming Wang, Benedicte Sammut, Jolene J Windle, G. David Roodman, Aliye Sarmasik, Yuko Hiruma, Quanhong Sun, Deborah L GalsonAbstract:Measles Virus plays an important role as an environmental factor in the pathogenesis of Paget's disease (PD). Previous studies have shown that IL-6 is increased in the bone marrow of Paget's patients and that measles Virus Nucleocapsid protein (MVNP) induces IL-6 secretion by pagetic osteoclasts. Further, IL-6 plays a critical role in the development of pagetic osteoclasts and bone lesions induced by PD, but the mechanisms regulating IL-6 production by MVNP remain unclear. Our current studies revealed that MVNP expression in osteoclast precursors down-regulated Sirt1 mRNA and protein, a negative regulator of NF-κB activity, which is a key factor for IL-6 expression. MVNP expression in NIH3T3 cells also elevated Il-6 transcription and impaired the expression of Sirt1 mRNA both under basal conditions and upon activation of the Sirt1 upstream regulator FoxO3 by LY294002 (a PI3K/AKT inhibitor). Luciferase activity assays showed that constitutively active FoxO3 abolished the repressive effect of MVNP on reporters driven by either FoxO3 response elements or the Sirt1 promoter. Further, protein stability assays revealed that FoxO3 was degraded more rapidly in MVNP-expressing cells than in control cells following the addition of cycloheximide. Similarly, co-transfection of MVNP and FoxO3 into HEK293 cells demonstrated that MVNP decreased the protein levels of over-expressed FoxO3 in a dose-dependent manner. Treatment with the proteasome inhibitor, MG132, blocked the MVNP-triggered decrease of FoxO3, and the treatment with the serine/threonine phosphatase inhibitor, calyculin A, revealed that MVNP increased phosphorylation of FoxO3. Further, over-expression of Sirt1 or treatment with the Sirt1 activator resveratrol blocked the increase in Il-6 transcription by MVNP. Finally, resveratrol reduced the numbers of TRAP positive multi-nuclear cells in bone marrow cultures from TRAP-MVNP transgenic mice to wild type levels. These results indicate that MVNP decreases FoxO3/Sirt1 signaling to enhance the levels of IL-6, which in part mediate MVNP's contribution to the development of Paget's disease.
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contributions of the measles Virus Nucleocapsid gene and the sqstm1 p62p392l mutation to paget s disease
Cell Metabolism, 2011Co-Authors: Noriyoshi Kurihara, Deborah L Galson, Yuko Hiruma, Jumpei Teramachi, Laëtitia Michou, Kei Yamana, Côme Rousseau, Jean Morissette, Hua Zhou, David W. DempsterAbstract:Summary Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high IL-6 levels and induce exuberant bone formation. Because measles Virus Nucleocapsid gene (MVNP) and the p62 P392L mutation are implicated in PD, marrows from 12 PD patients harboring p62 P392L and eight normals were tested for MVNP expression and pagetic OCL formation. Eight out of twelve patients expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense-MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice expressing only p62 P394L formed normal OCL, while mice expressing MVNP in OCL, with or without p62 P394L , developed pagetic OCL and expressed high IL-6 levels dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic OCL development in vitro. Mice coexpressing MVNP and p62 P394L developed dramatic Paget's-like bone lesions. These results suggest that p62 P394L and IL-6 induction by MVNP play key roles in PD.
Noriyoshi Kurihara - One of the best experts on this subject based on the ideXlab platform.
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measles Virus Nucleocapsid protein increases osteoblast differentiation in paget s disease
Journal of Clinical Investigation, 2016Co-Authors: Jumpei Teramachi, Jolene J Windle, Yuki Nagata, Khalid S. Mohammad, Yuji Inagaki, Yasuhisa Ohata, Theresa A. Guise, Laëtitia Michou, Jacques P. Brown, Noriyoshi KuriharaAbstract:Paget's disease (PD) is characterized by focal and dramatic bone resorption and formation. Treatments that target osteoclasts (OCLs) block both pagetic bone resorption and formation; therefore, PD offers key insights into mechanisms that couple bone resorption and formation. Here, we evaluated OCLs from 3 patients with PD and determined that measles Virus Nucleocapsid protein (MVNP) was expressed in 70% of these OCLs. Moreover, transgenic mice with OCL-specific expression of MVNP (MVNP mice) developed PD-like bone lesions that required MVNP-dependent induction of high IL-6 expression levels in OCLs. In contrast, mice harboring a knockin of p62P394L (p62-KI mice), which is the most frequent PD-associated mutation, exhibited increased bone resorption, but not formation. Evaluation of OCLs from MVNP, p62-KI, and WT mice revealed increased IGF1 expression in MVNP-expressing OCLs that resulted from the high IL-6 expression levels in these cells. IL-6, in turn, increased the expression of coupling factors, specifically ephrinB2 on OCLs and EphB4 on osteoblasts (OBs). IGF1 enhanced ephrinB2 expression on OCLs and OB differentiation. Importantly, ephrinB2 and IGF1 levels were increased in MVNP-expressing OCLs from patients with PD and MVNP-transduced human OCLs compared with levels detected in controls. Further, anti-IGF1 or anti-IGF1R blocked Runx2 and osteocalcin upregulation in OBs cocultured with MVNP-expressing OCLs. These results suggest that in PD, MVNP upregulates IL-6 and IGF1 in OCLs to increase ephrinB2-EphB4 coupling and bone formation.
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Measles Virus Nucleocapsid protein increases osteoblast differentiation in Paget’s disease
Journal of Clinical Investigation, 2016Co-Authors: Jumpei Teramachi, Jolene J Windle, Yuki Nagata, Khalid S. Mohammad, Yuji Inagaki, Yasuhisa Ohata, Theresa A. Guise, Laëtitia Michou, Jacques P. Brown, Noriyoshi KuriharaAbstract:Paget's disease (PD) is characterized by focal and dramatic bone resorption and formation. Treatments that target osteoclasts (OCLs) block both pagetic bone resorption and formation; therefore, PD offers key insights into mechanisms that couple bone resorption and formation. Here, we evaluated OCLs from 3 patients with PD and determined that measles Virus Nucleocapsid protein (MVNP) was expressed in 70% of these OCLs. Moreover, transgenic mice with OCL-specific expression of MVNP (MVNP mice) developed PD-like bone lesions that required MVNP-dependent induction of high IL-6 expression levels in OCLs. In contrast, mice harboring a knockin of p62P394L (p62-KI mice), which is the most frequent PD-associated mutation, exhibited increased bone resorption, but not formation. Evaluation of OCLs from MVNP, p62-KI, and WT mice revealed increased IGF1 expression in MVNP-expressing OCLs that resulted from the high IL-6 expression levels in these cells. IL-6, in turn, increased the expression of coupling factors, specifically ephrinB2 on OCLs and EphB4 on osteoblasts (OBs). IGF1 enhanced ephrinB2 expression on OCLs and OB differentiation. Importantly, ephrinB2 and IGF1 levels were increased in MVNP-expressing OCLs from patients with PD and MVNP-transduced human OCLs compared with levels detected in controls. Further, anti-IGF1 or anti-IGF1R blocked Runx2 and osteocalcin upregulation in OBs cocultured with MVNP-expressing OCLs. These results suggest that in PD, MVNP upregulates IL-6 and IGF1 in OCLs to increase ephrinB2-EphB4 coupling and bone formation.
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TBK1 mediates critical effects of measles Virus Nucleocapsid protein (MVNP) on pagetic osteoclast formation.
Journal of Bone and Mineral Research, 2013Co-Authors: Benedicte Sammut, Noriyoshi Kurihara, Feng-ming Wang, Jolene J Windle, G. David Roodman, Deborah L GalsonAbstract:Paget's disease of bone (PDB) is characterized by abnormal osteoclasts with unique characteristics that include increased sensitivity of osteoclast progenitors to 1,25(OH)2D3, receptor activator of NF-κB ligand (RANKL), and TNF-α; increased osteoclast numbers; and increased expression of IL-6 and several transcription factors. We recently reported that measles Virus Nucleocapsid protein (MVNP) plays a key role in the development of these abnormal osteoclasts. MVNP can induce the pagetic osteoclast phenotype in vitro and in vivo in TRAP-MVNP transgenic mice. However, the molecular mechanisms by which MVNP generates pagetic osteoclasts have not been determined. TANK-binding kinase 1 (TBK1) and IκB kinase-ϵ (IKKϵ) are IKK family members that complex with MVNP and activate both IRF3 and NF-κB pathways. MVNP increases the amount of TBK1 protein in bone marrow monocytes (BMM). Interestingly, we found that RANKL increased TBK1 and IKKϵ early in osteoclast differentiation, suggesting a possible role in normal osteoclastogenesis. However, only TBK1 is further increased in osteoclasts formed by TRAP-MVNP BMM owing to increased TBK1 protein stability. TBK1 overexpression induced IL6 promoter reporter activity, and elevated endogenous IL6 mRNA and p65 NF-κB, TAF12, and ATF7 proteins in several cell lines. Overexpression of TBK1 was insufficient to induce pagetic osteoclasts from WT BMM but synergized with MVNP to increase pagetic osteoclast formation from TRAP-MVNP BMM. BX795 inhibition of TBK1 impaired MVNP-induced IL-6 expression in both NIH3T3 cells and BMM, and shRNA knockdown of Tbk1 in NIH3T3 cells impaired IL-6 secretion induced by MVNP and decreased TAF12 and ATF7, factors involved in 1,25(OH)2D3 hypersensitivity of pagetic osteoclasts. Similarly, Tbk1 knockdown in BMM from TRAP-MVNP and WT mice specifically impaired development of the MVNP-induced osteoclast pagetic phenotype. These results demonstrate that TBK1 plays a critical role in mediating the effects of MVNP on osteoclast differentiation and on the expression of IL-6, a key contributor to the pagetic osteoclast phenotype. © 2014 American Society for Bone and Mineral Research.
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TBK1 mediates critical effects of measles Virus Nucleocapsid protein (MVNP) on pagetic osteoclast formation.
Journal of Bone and Mineral Research, 2013Co-Authors: Quanhong Sun, Noriyoshi Kurihara, Benedicte Sammut, Feng-ming Wang, Jolene J Windle, G. David Roodman, Deborah L GalsonAbstract:Paget's disease of bone (PDB) is characterized by abnormal osteoclasts with unique characteristics that include increased sensitivity of osteoclast progenitors to 1,25(OH)2 D3 , receptor activator of NF-κB ligand (RANKL), and TNF-α; increased osteoclast numbers; and increased expression of IL-6 and several transcription factors. We recently reported that measles Virus Nucleocapsid protein (MVNP) plays a key role in the development of these abnormal osteoclasts. MVNP can induce the pagetic osteoclast phenotype in vitro and in vivo in TRAP-MVNP transgenic mice. However, the molecular mechanisms by which MVNP generates pagetic osteoclasts have not been determined. TANK-binding kinase 1 (TBK1) and IκB kinase-ϵ (IKKϵ) are IKK family members that complex with MVNP and activate both IRF3 and NF-κB pathways. MVNP increases the amount of TBK1 protein in bone marrow monocytes (BMM). Interestingly, we found that RANKL increased TBK1 and IKKϵ early in osteoclast differentiation, suggesting a possible role in normal osteoclastogenesis. However, only TBK1 is further increased in osteoclasts formed by TRAP-MVNP BMM owing to increased TBK1 protein stability. TBK1 overexpression induced IL6 promoter reporter activity, and elevated endogenous IL6 mRNA and p65 NF-κB, TAF12, and ATF7 proteins in several cell lines. Overexpression of TBK1 was insufficient to induce pagetic osteoclasts from WT BMM but synergized with MVNP to increase pagetic osteoclast formation from TRAP-MVNP BMM. BX795 inhibition of TBK1 impaired MVNP-induced IL-6 expression in both NIH3T3 cells and BMM, and shRNA knockdown of Tbk1 in NIH3T3 cells impaired IL-6 secretion induced by MVNP and decreased TAF12 and ATF7, factors involved in 1,25(OH)2 D3 hypersensitivity of pagetic osteoclasts. Similarly, Tbk1 knockdown in BMM from TRAP-MVNP and WT mice specifically impaired development of the MVNP-induced osteoclast pagetic phenotype. These results demonstrate that TBK1 plays a critical role in mediating the effects of MVNP on osteoclast differentiation and on the expression of IL-6, a key contributor to the pagetic osteoclast phenotype.
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contributions of the measles Virus Nucleocapsid gene and the sqstm1 p62p392l mutation to paget s disease
Cell Metabolism, 2011Co-Authors: Noriyoshi Kurihara, Deborah L Galson, Yuko Hiruma, Jumpei Teramachi, Laëtitia Michou, Kei Yamana, Côme Rousseau, Jean Morissette, Hua Zhou, David W. DempsterAbstract:Summary Paget's disease (PD) is characterized by abnormal osteoclasts (OCL) that secrete high IL-6 levels and induce exuberant bone formation. Because measles Virus Nucleocapsid gene (MVNP) and the p62 P392L mutation are implicated in PD, marrows from 12 PD patients harboring p62 P392L and eight normals were tested for MVNP expression and pagetic OCL formation. Eight out of twelve patients expressed MVNP and formed pagetic OCL in vitro, which were inhibited by antisense-MVNP. Four out of twelve patients lacked MVNP and formed normal OCL that were hyperresponsive to RANKL but unaffected by antisense-MVNP. Similarly, mice expressing only p62 P394L formed normal OCL, while mice expressing MVNP in OCL, with or without p62 P394L , developed pagetic OCL and expressed high IL-6 levels dependent on p38MAPK activation. IL-6 deficiency in MVNP mice abrogated pagetic OCL development in vitro. Mice coexpressing MVNP and p62 P394L developed dramatic Paget's-like bone lesions. These results suggest that p62 P394L and IL-6 induction by MVNP play key roles in PD.
Tomasz I Michalak - One of the best experts on this subject based on the ideXlab platform.
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persistence of isolated antibodies to woodchuck hepatitis Virus core antigen is indicative of occult infection
Hepatology, 2004Co-Authors: Carla S Coffin, Tram N Q Pham, Patricia M Mulrooney, Norma D Churchill, Tomasz I MichalakAbstract:Antibodies against Virus Nucleocapsid (anticore) normally accompany hepadnaviral hepatitis but they may also occur in the absence of symptoms and other serological indicators of the infection. This situation can be encountered following a clinically and serologically unapparent exposure to hepatitis B Virus (HBV) or after recovery from hepatitis B. In this study, woodchucks inoculated with woodchuck hepatitis Virus (WHV) were investigated to determine the relationship between anticore detection and the molecular status of Virus replication in a primary WHV surface antigen (WHsAg)-negative infection or long-after resolution of WHV hepatitis. Serial, parallel samples of sera, peripheral blood mononuclear cells (PBMC) and liver tissue, collected for more than 5 years after inoculation with Virus, were examined for WHV DNA by highly sensitive polymerase chain reaction (PCR)/nucleic acid hybridization assays. Sera were also tested for WHV DNA after DNase treatment and for WHV DNA and WHsAg after concentration in sucrose. Liver and PBMC were examined for WHV covalently closed circular DNA and viral RNA transcripts by PCR-based techniques to assess Virus replication status. The study showed that anticore antibodies existing in the absence of other serological markers are a reliable indicator of occult WHV infection. This state can be accompanied by traces of circulating particles behaving as intact virions and by intermittent minimal-to-mild liver inflammation. In conclusion, the long-term presence of anticore antibodies alone is a consequence of sustained restimulation of the immune system by Virus Nucleocapsid produced during low-level hepadnaviral assembly. (HEPATOLOGY 2004.)
Florian Schodel - One of the best experts on this subject based on the ideXlab platform.
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Immunization with recombinant woodchuck hepatitis Virus Nucleocapsid antigen or hepatitis B Virus Nucleocapsid antigen protects woodchucks from woodchuck hepatitis Virus infection.
Vaccine, 2002Co-Authors: Florian Schodel, Darrell L Peterson, Georg Neckermann, Steve Fuller, Hans Will, Klaus Fuchs, Michael RoggendorfAbstract:Woodchucks were immunized with recombinant woodchuck hepatitis Virus (WHV) Nucleocapsid antigen (WHcAg) or hepatitis B Virus (HBV) Nucleocapsid antigen (HBcAg) and challenged with 106 WHV ID50. Six out of six woodchucks immunized with WHcAg and four out of six immunized with HBcAg were protected from WHV infection. Woodchucks immunized with WHcAg or HBcAg developed high serum antibody titres against WHcAg or HBcAg. Antibodies against WHc and HBc displayed little cross-reactivity (
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immunization with recombinant woodchuck hepatitis Virus Nucleocapsid antigen or hepatitis b Virus Nucleocapsid antigen protects woodchucks from woodchuck hepatitis Virus infection
Vaccine, 1993Co-Authors: Florian Schodel, Darrell L Peterson, Georg Neckermann, Steve Fuller, Hans Will, Klaus Fuchs, Michael RoggendorfAbstract:Woodchucks were immunized with recombinant woodchuck hepatitis Virus (WHV) Nucleocapsid antigen (WHcAg) or hepatitis B Virus (HBV) Nucleocapsid antigen (HBcAg) and challenged with 106 WHV ID50. Six out of six woodchucks immunized with WHcAg and four out of six immunized with HBcAg were protected from WHV infection. Woodchucks immunized with WHcAg or HBcAg developed high serum antibody titres against WHcAg or HBcAg. Antibodies against WHc and HBc displayed little cross-reactivity (<1%). This confirms and extends previous reports of protection against homologous challenge after immunization with HBcAg/WHcAg which are both internal viral antigens. As the dominant B-cell epitope(s) on particulate WHcAg and HBcAg appear not to be conserved it also demonstrates that antibodies against HBcAg/WHcAg are not important for this protection. Woodchucks immunized with WHcAg/HBcAg reacted with a fast serum antibody response against viral envelope proteins upon challenge with WHV, indicative of functional intrastructural/intermolecular T-cell help as one potential mechanism of protection after immunization with an internal viral antigen.
