scholarly journals Gene Expression Profiling Indicates the Roles of Host Oxidative Stress, Apoptosis, Lipid Metabolism, and Intracellular Transport Genes in the Replication of Hepatitis C Virus

2010 ◽  
Vol 84 (10) ◽  
pp. 5404-5414 ◽  
Author(s):  
Samantha Blackham ◽  
Andrew Baillie ◽  
Fadel Al-Hababi ◽  
Katja Remlinger ◽  
Shihyun You ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Lipid Metabolism ◽  
Hepatitis C ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Intracellular Transport ◽  
Hcv Infection ◽  
Replication Cycle ◽  
Host Genes

ABSTRACT Hepatitis C virus (HCV) is a leading cause of chronic liver disease. The identification and characterization of key host cellular factors that play a role in the HCV replication cycle are important for the understanding of disease pathogenesis and the identification of novel antiviral therapeutic targets. Gene expression profiling of JFH-1-infected Huh7 cells by microarray analysis was performed to identify host cellular genes that are transcriptionally regulated by infection. The expression of host genes involved in cellular defense mechanisms (apoptosis, proliferation, and antioxidant responses), cellular metabolism (lipid and protein metabolism), and intracellular transport (vesicle trafficking and cytoskeleton regulation) was significantly altered by HCV infection. The gene expression patterns identified provide insight into the potential mechanisms that contribute to HCV-associated pathogenesis. These include an increase in proinflammatory and proapoptotic signaling and a decrease in the antioxidant response pathways of the infected cell. To investigate whether any of the host genes regulated by infection were required by HCV during replication, small interfering RNA (siRNA) silencing of host gene expression in HCV-infected cells was performed. Decreasing the expression of host genes involved in lipid metabolism (TXNIP and CYP1A1 genes) and intracellular transport (RAB33b and ABLIM3 genes) reduced the replication and secretion of HCV, indicating that they may be important factors for the virus replication cycle. These results show that major changes in the expression of many different genes in target cells may be crucial in determining the outcome of HCV infection.

scholarly journals Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 36
Author(s):  
Christopher Dächert ◽  
Evgeny Gladilin ◽  
Marco Binder
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gene Expression Profiling ◽  
Cell Line ◽  
Expression Profiling ◽  
Hepatoma Cell ◽  
Host Factors ◽  
Hepatoma Cell Line ◽  
Huh7 Cells

Chronic Hepatitis C virus (HCV) infection still constitutes a major global health problem with almost half a million deaths per year. To date, the human hepatoma cell line Huh7 and its derivatives is the only cell line that robustly replicates HCV. However, even different subclones and passages of this single cell line exhibit tremendous differences in HCV replication efficiency. By comparative gene expression profiling using a multi-pronged correlation analysis across eight different Huh7 variants, we identified 34 candidate host factors possibly affecting HCV permissiveness. For seven of the candidates, we could show by knock-down studies their implication in HCV replication. Notably, for at least four of them, we furthermore found that overexpression boosted HCV replication in lowly permissive Huh7 cells, most prominently for the histone-binding transcriptional repressor THAP7 and the nuclear receptor NR0B2. For NR0B2, our results suggest a finely balanced expression optimum reached in highly permissive Huh7 cells, with even higher levels leading to a nearly complete breakdown of HCV replication, likely due to a dysregulation of bile acid and cholesterol metabolism. Our unbiased expression-profiling approach, hence, led to the identification of four host cellular genes that contribute to HCV permissiveness in Huh7 cells. These findings add to an improved understanding of the molecular underpinnings of the strict host cell tropism of HCV.

Gene Expression Profiling of Immune Responsive and Fibrosis Genes in Hepatitis C Virus Infected Patients

2014 ◽  
Vol 27 (5) ◽  
pp. 250-254 ◽  
Author(s):  
Sobia Idrees ◽  
Usman Ali Ashfaq ◽  
Muhammad Shareef Masoud ◽  
Muhammad Qasim ◽  
Tariq Javed ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Gene Expression Profiling ◽  
Expression Profiling

scholarly journals Novel Cell-Based Hepatitis C Virus Infection Assay for Quantitative High-Throughput Screening of Anti-Hepatitis C Virus Compounds

2013 ◽  
Vol 58 (2) ◽  
pp. 995-1004 ◽  
Author(s):  
Zongyi Hu ◽  
Keng-Hsin Lan ◽  
Shanshan He ◽  
Manju Swaroop ◽  
Xin Hu ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Throughput ◽  
High Throughput Screening ◽  
Dose Range ◽  
Hcv Infection ◽  
Replication Cycle ◽  
Screening Methods ◽  
Functional Features ◽  
Pharmacologically Active

ABSTRACTTherapy for hepatitis C virus (HCV) infection has advanced with the recent approval of direct-acting antivirals in combination with peginterferon and ribavirin. New antivirals with novel targets are still needed to further improve the treatment of hepatitis C. Previously reported screening methods for HCV inhibitors either are limited to a virus-specific function or apply a screening method at a single dose, which usually leads to high false-positive or -negative rates. We developed a quantitative high-throughput screening (qHTS) assay platform with a cell-based HCV infection system. This highly sensitive assay can be miniaturized to a 1,536-well format for screening of large chemical libraries. All candidates are screened over a 7-concentration dose range to give EC50s (compound concentrations at 50% efficacy) and dose-response curves. Using this assay format, we screened a library of pharmacologically active compounds (LOPAC). Based on the profile of dose-dependent curves of HCV inhibition and cytotoxicity, 22 compounds with adequate curves and EC50s of <10 μM were selected for validation. In two additional independent assays, 17 of them demonstrated specific inhibition of HCV infection. Ten potential candidates with efficacies of >70% and CC50s (compound concentrations at 50% cytotoxicity) of <30 μM from these validated hits were characterized for their target stages in the HCV replication cycle. In this screen, we identified both known and novel hits with diverse structural and functional features targeting various stages of the HCV replication cycle. The pilot screen demonstrates that this assay system is highly robust and effective in identifying novel HCV inhibitors and that it can be readily applied to large-scale screening of small-molecule libraries.

scholarly journals Gene Expression Profiling Specifies Chemokine, Mitochondrial and Lipid Metabolism Signatures in Leprosy

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e64748 ◽  
Author(s):  
Luana Tatiana Albuquerque Guerreiro ◽  
Anna Beatriz Robottom-Ferreira ◽  
Marcelo Ribeiro-Alves ◽  
Thiago Gomes Toledo-Pinto ◽  
Tiana Rosa Brito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Gene Expression Profiling ◽  
Expression Profiling

scholarly journals Inhibition of STAT Pathway Impairs Anti-Hepatitis C Virus Effect of Interferon Alpha

2016 ◽  
Vol 40 (1-2) ◽  
pp. 77-90 ◽  
Author(s):  
Lan-Juan Zhao ◽  
Sheng-Fei He ◽  
Yuan Liu ◽  
Ping Zhao ◽  
Zhong-Qi Bian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Alpha ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Jak Inhibitor ◽  
Stat Signaling ◽  
Antiviral Gene ◽  
Stat Pathway

Background/Aims: Signal transducer and activator of transcription (STAT) pathway plays an important role in antiviral efficacy of interferon alpha (IFN-α). IFN-α is the main therapeutic against hepatitis C virus (HCV) infection. We explored effects of IFN-α on HCV replication and antiviral gene expression by targeting STAT. Methods: In response to IFN-α, STAT status, HCV replication, and antiviral gene expression were analyzed in human hepatoma Huh7.5.1 cells before and after cell culture-derived HCV infection. Results: IFN-α treatment induced expression and phosphorylation of STAT1 and STAT2 in Huh7.5.1 cells. Pretreatment of Huh7.5.1 cells with a mAb to IFN alpha receptor (IFNAR) 2 decreased IFN-α-dependent phosphorylation of STAT1 and STAT2, whereas pretreatment with an IFNAR1 mAb increased such phosphorylation, suggesting that IFNAR mediates IFN-α-triggered STAT signaling. During HCV infection, STAT1 and STAT2 phosphorylation could be rescued by IFN-α and IFN-α-induced phosphorylation of STAT1 and STAT2 was impaired. Inhibition of STAT pathway by Jak inhibitor I significantly enhanced HCV RNA replication and viral protein expression. Antiviral genes coding for IFN regulatory factor 9 and IFN-stimulated gene 15 were up-regulated by IFN-α during HCV infection but such up-regulation was abrogated by Jak inhibitor I. Conclusion: These results establish that activation of STAT pathway is essential for anti-HCV efficacy of IFN-α. Impairment of IFN-α-triggered STAT signaling by HCV may account for evading IFN-α response.

scholarly journals Evaluation of Serum and Gene Expression of Galectin-4, Interleukin-27, and Complement-7 in Hepatitis C Virus-Infected Egyptian Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Marwa S. Abdel-Tawab ◽  
Hanan H. Fouad ◽  
Dalia A. Omran ◽  
Aml E. Abdou ◽  
Shaimaa Mohamed Zaied ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis C Virus ◽  
Viral Load ◽  
Hepatitis C ◽  
Serum Proteins ◽  
Serum Levels ◽  
Hcv Infection ◽  
Expression Levels ◽  
Interleukin 27 ◽  
Gene Expression Levels

Background. Hepatitis C virus (HCV) is considered a major global public health problem. Recently, there are great advances in HCV therapy, but there are some limitations that are creating an urgent need for assessment of some cytokines that have a potent antiviral effect in the immune system and anti-inflammatory effects to provide a potential novel immunotherapeutic target in HCV infection. Objective. This study was directed to assess the serum levels and gene expression levels of Galectin-4 (LEG4), Interleukin-27 (IL-27), and Complement-7 (C-7) and their correlation with the viral load in HCV infection. Subjects and Methods. This work was conducted on 80 subjects, Group 1 ( n = 40 ) early detected HCV patients and Group 2 ( n = 40 ) healthy controls. LEG4, IL-27, and C-7 were assessed at the protein levels by ELISA, and their gene expression was assessed by RT-qPCR. The viral load was measured by PCR. Results. There were significant elevations in the mean levels of gene expression and serum levels of all studied parameters LEG4, IL-27, and C-7 in the HCV group compared to the control group. Significant negative correlations between the viral load and each of the serum proteins and gene expressions of both LEG4 and IL-27 in HCV patients were found. The gene expression levels of LEG4, IL-27, and C-7 were positively correlated with their corresponding serum proteins in HCV patients.Conclusion. LEG4 and IL-27 showed significant negative correlations with the viral load, which could be an immune response to the control of the extent of hepatic inflammation, thus creating a potential novel immunotherapeutic approach in HCV infection for further studies or therapeutic clinical trials.

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