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Infectious Disease: Hepatitis C

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Total 109 results found since Jan 2013.

Interferon alpha (IFNα)-induced TRIM22 interrupts HCV replication by ubiquitinating NS5A.
Abstract TRIM22, a tripartite-motif (TRIM) protein, is upregulated upon interferon alpha (IFNα) administration to hepatitis C virus (HCV)-infected patients. However, the physiological role of TRIM22 upregulation remains unclear. Here, we describe a potential antiviral function of TRIM22's targeting of the HCV NS5A protein. NS5A is important for HCV replication and for resistance to IFNα therapy. During the first 24 h following the initiation of IFNα treatment, upregulation of TRIM22 in the peripheral blood mononuclear cells (PBMCs) of HCV patients correlated with a decrease in viral titer. This phenomenon was ...
Source: Cellular and Molecular Immunology - February 16, 2015 Category: Molecular Biology Authors: Yang C, Zhao X, Sun D, Yang L, Chong C, Pan Y, Chi X, Gao Y, Wang M, Shi X, Sun H, Lv J, Gao Y, Zhong J, Niu J, Sun B Tags: Cell Mol Immunol Source Type: research

Antiviral and Immunoregulatory Effects of Indoleamine-2,3-Dioxygenase in Hepatitis C Virus Infection
In patients with hepatitis C virus (HCV) infection, enhanced activity of indoleamine-2,3-dioxygenase 1 (IDO) has been reported. IDO - a tryptophan-catabolizing enzyme - has been considered as both an innate defence mechanism and an important regulator of the immune response. The molecular mechanism of IDO induction in HCV infection and its role in the antiviral immune response remain unknown. Using primary human hepatocytes, we show that HCV infection stimulates IDO expression. IDO gene induction was transient and coincided with the expression of types I and III interferons (IFNs) and IFN-stimulated genes in HCV-infected h...
Source: Journal of Innate Immunity - March 19, 2015 Category: Allergy & Immunology Source Type: research

Lipopolysaccharide (LPS)-Induced Biliary Epithelial Cell NRas Activation Requires Epidermal Growth Factor Receptor (EGFR)
by Christy E. Trussoni, James H. Tabibian, Patrick L. Splinter, Steven P. O’Hara Cholangiocytes (biliary epithelial cells) actively participate in microbe-induced proinflammatory responses in the liver and contribute to inflammatory and infectious cholangiopathies. We previously demonstrated that cholangiocyte TLR-dependent NRas activation contributes to proinflammatory/ proliferative responses. We test the hypothesis that LPS-induced activation of NRas requires the EGFR. SV40-transformed human cholangiocytes (H69 cells), or low passage normal human cholangiocytes (NHC), were treated with LPS in the presence or absence ...
Source: PLoS One - April 27, 2015 Category: Biomedical Science Authors: Christy E. Trussoni et al. Source Type: research

New and Emerging Agents for the Treatment of Hemophilia: Focus on Extended Half-Life Recombinant Clotting Proteins
Abstract Hemophilia A and B are X-linked disorders caused by deficient or defective clotting factor VIII (FVIII) or IX factor (FIX) proteins, and characterized by spontaneous or traumatic bleeding into joints and muscles. Previous use of plasma and plasma-derived clotting factors that lacked appropriate viral inactivation steps in manufacturing led to significant morbidity associated with transfusion-transmitted HIV and hepatitis C virus (HCV). The development of recombinant proteins revolutionized their treatment, and, with no new HIV or HCV infection via clotting proteins for nearly 30 years, greatly improved t...
Source: Drugs - August 27, 2015 Category: Drugs & Pharmacology Source Type: research

Heterogeneous ribonucleoprotein K (hnRNP K) binds miR-122, a mature liver-specific microRNA required for hepatitis C virus replication.
Abstract Heterogeneous ribonucleoprotein K (hnRNP K) binds to the 5' untranslated region of the hepatitis C virus (HCV) and is required for HCV RNA replication. The hnRNP K binding site on HCV RNA overlaps with the sequence recognized by the liver-specific microRNA, miR-122. A proteome chip containing ~17,000 unique human proteins probed with miR-122 identified hnRNP K as one of the strong binding proteins. In vitro kinetic study showed hnRNP K binds miR-122 with a nanomolar dissociation constant, in which the short pyrimidine-rich residues in the central and 3' portion of the miR-122 were required for hnRNP K bin...
Source: Molecular and Cellular Proteomics : MCP - September 1, 2015 Category: Molecular Biology Authors: Fan B, Sutandy FX, Syu GD, Middleton S, Yi G, Lu KY, Chen CS, Kao CC Tags: Mol Cell Proteomics Source Type: research

SUMO1 depletion prevents lipid droplet accumulation and HCV replication
Abstract Infection by hepatitis C virus (HCV) is a major public-health problem. Chronic infection often leads to cirrhosis, steatosis, and hepatocellular carcinoma. The life cycle of HCV depends on the host cell machinery and involves intimate interaction between viral and host proteins. However, the role of host proteins in the life cycle of HCV remains poorly understood. Here, we identify the small ubiquitin-related modifier (SUMO1) as a key host factor required for HCV replication. We performed a series of cell biology and biochemistry experiments using the HCV JFH-1 (Japanese fulminate hepatitis 1) genotype 2a...
Source: Archives of Virology - October 8, 2015 Category: Virology Source Type: research

HCV-activated NLRP3 Inflammasome Regulates Lipid Metabolism Molecular Bases of Disease
In this study, we elucidate the potential link between chronic hepatitis C-associated inflammation and alteration of lipid homeostasis in infected cells. Our results reveal that the HCV-activated NLRP3 inflammasome is required for the up-regulation of lipogenic genes such as 3-hydroxy-3-methylglutaryl-coenzyme A synthase, fatty acid synthase, and stearoyl-CoA desaturase. Using pharmacological inhibitors and siRNA against the inflammasome components (NLRP3, apoptosis-associated speck-like protein containing a CARD, and caspase-1), we further show that the activation of the NLRP3 inflammasome plays a critical role in lipid d...
Source: Journal of Biological Chemistry - February 12, 2016 Category: Chemistry Authors: McRae, S., Iqbal, J., Sarkar-Dutta, M., Lane, S., Nagaraj, A., Ali, N., Waris, G. Tags: Microbiology Source Type: research

Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation.
Abstract Hepatitis C virus (HCV) NS5A protein is essential for HCV RNA replication and virus assembly. Here we report the identification of NS5A phosphorylation sites Ser-222, Ser-235 and Thr-348 during an infectious HCV replication cycle and demonstrate that Ser-235 phosphorylation is essential for HCV RNA replication. Confocal microscopy revealed that both phosphoablatant (S235A) and phosphomimetic (S235D) mutants redistribute NS5A to large juxta-nuclear foci that display altered colocalization with known replication complex components. Using electron microscopy (EM) we found that S235D alters virus-induced memb...
Source: Virology - February 10, 2016 Category: Virology Authors: Eyre NS, Hampton-Smith RJ, Aloia AL, Eddes JS, Simpson KJ, Hoffmann P, Beard MR Tags: Virology Source Type: research

Enhancement of the replication of HCV replicons of genotypes 1-4 by manipulation of CpG and UpA dinucleotide frequencies and use of cell lines expressing SECL14L2 - application for antiviral resistance testing.
Abstract Treatment for hepatitis C virus (HCV) has improved greatly through the use of direct acting antivirals (DAAs). However, their effectiveness and potential for drug resistance development in non-genotype 1 variants of HCV remains relatively unexplored as in vitro assays to assess drug susceptibility are poorly developed and unsuited for a transient transfection format. In the current study, we have evaluated effects of dinucleotide frequency changes in the replicon and the use of a SEC14L2-expressing cell line on the replication of HCV of different genotypes and evaluated the resulting assay formats for sus...
Source: Antimicrobial Agents and Chemotherapy - March 7, 2016 Category: Microbiology Authors: Witteveldt J, Martin-Gans M, Simmonds P Tags: Antimicrob Agents Chemother Source Type: research

Assembly and release of infectious hepatitis C virus involving unusual organization of the secretory pathway.
CONCLUSION: Prior activity of the WNV subgenomic replicon in BHK-21 cells promoted re-wiring of host factors for the assembly and release of infectious HCV in a caspase-1-dependent mechanism. PMID: 27429716 [PubMed]
Source: World Journal of Hepatology - July 21, 2016 Category: Gastroenterology Tags: World J Hepatol Source Type: research

Acetaldehyde Disrupts Interferon Alpha Signaling in Hepatitis C Virus ‐Infected Liver Cells by Up‐Regulating USP18
ConclusionsWe conclude that Ach disrupts IFNα‐induced STAT1 phosphorylation by the up‐regulation of USP18 to block the innate immunity protection in HCV‐infected liver cells, thereby contributing to HCV‐alcohol pathogenesis. This, in part, may explain the mechanism of HCV‐infection exacerbation/progression in alcohol‐abusing patients. IFNα is an important innate immunity factor, which controls HCV replication and spread via the JAK‐STAT1 pathway activation. Here, we investigated the mechanisms which major ethanol metabolite, acetaldehyde, uses to enhance HCV RNA by decreasing IFNα‐induced STAT1 phosphor...
Source: Alcoholism: Clinical and Experimental Research - September 25, 2016 Category: Addiction Authors: Murali Ganesan, Larisa Y. Poluektova, Dean J. Tuma, Kusum K. Kharbanda, Natalia A. Osna Tags: Original Article Source Type: research

Efficient replication of blood borne Hepatitis C Virus in human fetal liver stem cells
Conclusion: Our data showed that the entire bbHCV life cycle could be naturally imitated in hFLSCs. This model is expected to provide a powerful tool for exploring the process and the mechanism of bbHCV infection at the cellular level, and evaluating the treatment and preventive strategies of bbHCV infection. This article is protected by copyright. All rights reserved.
Source: Hepatology - April 13, 2017 Category: Internal Medicine Authors: Xuan Guo, Shu Wang, Zhi ‐Gang Qiu, Ya‐Ling Dou, Wei‐Li Liu, Dong Yang, Zhi‐Qiang Shen, Zhao‐Li Chen, Jing‐Feng Wang, Bin‐ Zhang, Xin‐Wei Wang, Xiang‐Fei Guo, Xue‐Lian Zhang, Min Jin, Jun‐Wen Li Tags: Viral Hepatitis Source Type: research

Predominance of regorafenib over sorafenib: restoration of membrane ‐bound MICA in hepatocellular carcinoma cells
ConclusionsThe clinical superiority of REG over SOR is partially attributable to reduced MICA shedding via transcriptional suppression of ADAM9 and ADAM10.
Source: Journal of Gastroenterology and Hepatology - October 21, 2017 Category: Gastroenterology Authors: Jun Arai, Kaku Goto, Anthony Stephanou, Yasushi Tanoue, Sayaka Ito, Ryosuke Muroyama, Yasuo Matsubara, Ryo Nakagawa, Sayuri Morimoto, Yoshimi Kaise, Lay Ahyoung Lim, Hitoshi Yoshida, Naoya Kato Tags: Hepatology Source Type: research

Hepatitis C virus core protein-induced miR-93-5p up-regulation inhibits interferon signaling pathway by targeting IFNAR1.
CONCLUSION: HCV-1b core protein-induced miR-93-5p up-regulation inhibits the IFN signaling pathway by directly targeting IFNAR1, and the miR-93-5p-IFNAR1 axis regulates STAT1 phosphorylation. This axis may be a potential therapeutic target for HCV-1b infection. PMID: 29375208 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - January 14, 2018 Category: Gastroenterology Authors: He CL, Liu M, Tan ZX, Hu YJ, Zhang QY, Kuang XM, Kong WL, Mao Q Tags: World J Gastroenterol Source Type: research

Induction of Huh ‑7 cell apoptosis by HCV core proteins via CK1α‑p53‑Bid signaling pathway.
Induction of Huh‑7 cell apoptosis by HCV core proteins via CK1α‑p53‑Bid signaling pathway. Mol Med Rep. 2018 Apr 05;: Authors: Shen S, Li C, Dai M, Yan X Abstract Hepatitis C virus (HCV)‑infected liver cells sensitize host cells to tumor necrosis factor (TNF)‑related apoptosis‑inducing ligand (TRAIL)‑induced cell apoptosis; however, the precise mechanisms are unknown. In the present study, flow cytometry demonstrated that the Annexin V‑positive Huh‑7 cell number was higher in groups transfected with core proteins when compared with the pcDNA3.1 group. The mRNA and protein expression...
Source: Molecular Medicine Reports - April 6, 2018 Category: Molecular Biology Tags: Mol Med Rep Source Type: research