Nobuyuki Kato

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..Using this replicon cell culture system, it was demonstrated further that neither ribavirin nor its derivative mizoribine accelerated the mutation rate or the increase in the genetic diversity of HCV replicon...

..These results suggest that an HCV-RNA-replicating cell culture system would be useful for analysis of the evolutionary dynamics and variations of HCV...

..Taken together, present results indicate that the replicon RNA library generated using an in vitro HCV infection system is useful for the establishment of an HCV subgenomic replicon...

..The enormous body of information collected thus far in the field of HCV research is summarized below, and an overview of the current status of HCV molecular virology of HCV is provided...

..The OGF7 assay system is expected to be the most time-saving and inexpensive assay system for high-throughput screening of anti-HCV reagents...

..Geranylgeranyl pyrophosphate (GGPP) is a substrate for geranylgeranyltransferase. Therefore, we examined the potential of geranyl compounds with chemical structures similar to those of GGPP to inhibit HCV RNA replication...

..These newly established HCV replicon cell lines possessing IFN-resistant phenotypes are the first useful tools for understanding the mechanisms by which HCV acquires IFN resistance in vivo...

..CONCLUSIONS: The present results suggest that the epigenetic silencing of IFN-stimulated genes is implicated in the acquisition of a partially IFN-resistant phenotype of HCV replicon-harboring cells...

..Here, we demonstrated that NS5B of JFH-1 contributed to this strain's CsA-resistant phenotype. NS5B and CyPA are significant for determining HCV's sensitivity to CsA...

..This culture system is useful tool for the study of HCV replication and mass screening for anti-HCV reagents...

..Taken together, these results suggest that the ATM signaling pathway is critical for HCV RNA replication and may represent a novel target for the clinical treatment of patients with chronic hepatitis C...

..These results suggest that tandem repeats of LF-derived anti-HCV peptide are useful as anti-HCV reagents...

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..In combination with IFN, fluvastatin also exhibited a synergistic inhibitory effect. In conclusion, statins, especially fluvastatin, could be potentially useful as new anti-HCV reagents in combination with IFN...

..Reporter assay analysis suggests that the diverse effects of interferon-gamma are due to the difference in HCV strains, but not the cellular environment...

..Taken together, our findings suggest that the blocking of the interferon production by NS3-4A is not sufficient in HCV-infected hepatocyte cells...

..This modulation is one of the cellular responses that the GABA-B receptor modifies. This is the first report of microarray analysis applied to search inclusively for the target genes of LF...

..44 IU/ml vs. 1.37 IU/ml) and cyclosporine A (EC(50): 0.71 microg/ml vs. 0.96 microg/ml). These replicons are thus useful tools for examining the mechanism of anti-HCV activity, especially in IFN-lambda and statins...

..In conclusion, we demonstrated for the first time that inhibition of IMPDH is a major antiviral target by which RBV at clinically achievable concentrations inhibits HCV RNA replication...

..This is the first report to demonstrate that the core protein may disturb the DNA repair system...

..Our microarray analysis demonstrated that HCV subgenomic replicons can change the gene expression profiles of host cells, and it allowed us to compile the first list of genes that the replicons transcriptionally regulate...

..Thus, DDX3 is required for HCV RNA replication...

..Finally, Li23-derived cells persistently produced infectious virus of an HCV strain. Li23-derived cells are potentially useful for understanding the HCV life cycle and for finding antiviral targets...

..These findings suggest that specific viral factors may affect the replication level of genome-length HCV RNA...

..OSM is a candidate anti-HCV reagent and may improve the current IFN therapy for patients with chronic hepatitis C...

..Since mizoribine is currently used in several clinical applications and has not been associated with severe side effects, mizoribine is considered to be of potential use as a new anti-HCV reagent in combination with IFN-alpha...

..This intracellular modulation is expected to be a therapeutic target for the suppression of HCV RNA replication...

..5-year replication of HCV RNA. These genes may play roles in the optimization of the environment in HCV RNA replication, or may play key roles in the progression of HCV-associated hepatic diseases...

..These results suggest that the inhibitory effects of NS3-4A on antiviral signaling pathways are limited to the Cardif-mediated pathway in human hepatocytes...

..Moreover, it was shown that ectopic expression of wild-type IFNAR1 in IFN-resistant phenotype, replicon-harbouring cells possessing the IFNAR1 mutant restored type I IFN signalling...

..Retroviruses and some other enveloped viruses require an endosomal sorting complex required for transport (ESCRT) components and their associated proteins for their budding process...

..Taken together, these results suggest that the AH1R assay system is useful for the objective evaluation of anti-HCV reagents and for the discovery of different classes of anti-HCV reagents...

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..In this study, we developed HCV JFH-1 reporter-assay systems using two distinct hepatoma cell lines, HuH-7 and Li23. The mutations in NS5B resulted in different effects on strains O and JFH-1 HCV RNA replication...

..Taken together, these findings suggest that ATO inhibits the HCV RNA replication through modulation of the glutathione redox system and oxidative stress...

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..This cell culture system is expected to be a useful tool for vaccine development, as well as for further investigation of cellular factors that are essential for HCV RNA replication...

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..Our findings revealed that NS5B induced IFN-beta through the TLR3 signaling pathway in immortalized human hepatocytes even without replicating viral genomes...

..Furthermore, statins enhanced the anti-HCV effect of interferon in combination. Statins may be a promising candidate for the adjuvant in interferon therapy and may improve the efficiency of the current interferon and ribavirin therapy...

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..Finally, we also demonstrated that INI1 and DDX5, the PML-related proteins, are involved in HCV production. Taken together, these findings suggest that PML is required for HCV production...

..These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism...

..Thus anti-HCV reagents, which have a mechanism different from IFN-alpha, were shown to be useful for preventing a relapse of IFN-alpha-resistant HCV...

..These results led us to consider the development of an effective anti-HCV peptide. This is the first identification of a natural protein-derived peptide that specifically binds to HCV E2 protein and prevents HCV infection...

..Therefore, we conclude that plural HCV assay systems developed using different cell lines or HCV strains are required for the objective evaluation of anti-HCV reagents...

..The hypervariable region 1 found within the envelope E2 protein was shown to be a major site for the genetic evolution of HCV after the onset of hepatitis, and might be involved in escape from the host immunesurveillance system...

..The alteration in RBP expression was also confirmed by ELISA and Western blot analysis. We conclude that protein expression profiling demonstrated that HCV replicon eradication affected retinol-related protein expression...

..We demonstrated that this method was useful for the evaluation of antiviral reagents using HCV-infected human cultured cells...

..Further clinical trials showed that lactoferrin is a promising candidate for adjuvant therapy with interferon in patients with chronic hepatitis C...

..boidinii. To our knowledge, this is the first report on the gene coding for ASOD that can catalyze the oxidation of N-acetylated polyamine as a substrate, from any type of organism...

..5 microM). We then synthesized an analog of these compounds with optimized activity...

..Thus, the identification of more effective and better tolerated agents is a high priority. We applied chemical biology to screen small molecules that regulate HCV...

..Our results suggested that this mutation at least partly contributes to resistance to early viral clearance during interferon and ribavirin combination therapy...

..These results suggest that the HCV genome obtained from an in vitro HCV infection system with cultured cells can be used to develop a subgenomic replicon system with diverse HCV sequences...

..Moreover, the replication of HCV was activated. This phenomenon is detrimental to IFN therapy after liver transplantation, and the selection of calcineurin inhibitors may warrant further discussion depending on the transplant situation...

..Zinc supplementation thus appears to offer a novel approach to the development of future strategies for the treatment of intractable chronic hepatitis C...

..This study supports the development of IFN-alpha gene therapy for HCV-associated liver diseases...

..These findings provide an insight into the mechanisms of diversity governing virus-cell interactions and in the sensitivity of these strains to antiviral agents...

..We conclude that hepatocytes contain two distinct antiviral signaling pathways leading to expression of type I IFNs, one dependent upon TLR3 and the other dependent on RIG-I, with little cross-talk between these pathways...

..Our results collectively suggest the possibility that NS3 plays an important role in the hepatocarcinogenesis of HCV by interacting differentially with p53 in an NS3 sequence-dependent manner...

..Because an early and accurate diagnosis is necessary for proper management, radiologists should be familiar with the imaging features of each type of complication...

..The VSV pseudotypes developed here would be useful for analyzing the early stages of HCV infection...