Hepatitis C Virus-related Cirrhosis is a Major Determinant of the Expression Levels of Hepatic Drug Transporters

2010 ◽  
Vol 25 (2) ◽  
pp. 190-199 ◽  
Author(s):  
Ken Ogasawara ◽  
Tomohiro Terada ◽  
Toshiya Katsura ◽  
Etsuro Hatano ◽  
Iwao Ikai ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Drug Transporters ◽  
Major Determinant ◽  
Hepatic Drug ◽  
Expression Levels

Hepatitis C virus core protein promotes cell proliferation through the upregulation of cyclin E expression levels

2001 ◽  
Vol 21 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Jae-We Cho ◽  
Won-Ki Baek ◽  
Seong-Il Suh ◽  
Se-Hwan Yang ◽  
Jun Chang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Cyclin E ◽  
Expression Levels ◽  
Virus Core

scholarly journals Inhibitory Effect of a Triterpenoid Compound, with or without Alpha Interferon, on Hepatitis C Virus Infection

2011 ◽  
Vol 55 (6) ◽  
pp. 2537-2545 ◽  
Author(s):  
Takako Watanabe ◽  
Naoya Sakamoto ◽  
Mina Nakagawa ◽  
Sei Kakinuma ◽  
Yasuhiro Itsui ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Real Time ◽  
Interferon Regulatory Factor ◽  
Mechanisms Of Action ◽  
Alpha Interferon ◽  
Regulatory Factor ◽  
Rt Pcr ◽  
Response Element ◽  
Expression Levels

ABSTRACTA lack of patient response to alpha interferon (α-IFN) plus ribavirin (RBV) treatment is a major problem in eliminating hepatitis C virus (HCV). We screened chemical libraries for compounds that enhanced cellular responses to α-IFN and identified a triterpenoid, toosendanin (TSN). Here, we studied the effects and mechanisms of action of TSN on HCV replication and its effect on α-IFN signaling. We treated HCV genotype 1b replicon-expressing cells and HCV-J6/JFH-infected cells with TSN, with or without α-IFN, and the level of HCV replication was quantified. To study the effects of TSN on α-IFN signaling, we detected components of the interferon-stimulated gene factor 3 (ISGF3), phosphorylated signal transducer and activator of transcription 1 (STAT1), and STAT2 by Western blotting analysis; expression levels of mRNA of interferon regulatory factor 9 using real-time reverse transcription-PCR (RT-PCR); and interferon-stimulated response element reporter activity and measured the expression levels of interferon-inducible genes for 2′,5′-oligoadenylate synthetase, MxA, protein kinase R, and p56 using real-time RT-PCR. TSN alone specifically inhibited expression of the HCV replicon (50% effective concentration = 20.6 nM, 50% cytotoxic concentration > 3 μM, selectivity index > 146). Pretreatment with TSN prior to α-IFN treatment was more effective in suppressing HCV replication than treatment with either drug alone. Although TSN alone did not activate the α-IFN pathway, it significantly enhanced the α-IFN-induced increase of phosphorylated STATs, interferon-stimulated response element activation, and interferon-stimulated gene expression. TSN significantly increased baseline expression of interferon regulatory factor 9, a component of interferon-stimulated gene factor 3. Antiviral effects of treatment with α-IFN can be enhanced by pretreatment with TSN. Its mechanisms of action could potentially be important to identify novel molecular targets to treat HCV infection.

scholarly journals Protein Synthesis and Endoplasmic Reticulum Stress Can Be Modulated by the Hepatitis C Virus Envelope Protein E2 through the Eukaryotic Initiation Factor 2α Kinase PERK

2003 ◽  
Vol 77 (6) ◽  
pp. 3578-3585 ◽  
Author(s):  
Nicole Pavio ◽  
Patrick R. Romano ◽  
Thomas M. Graczyk ◽  
Stephen M. Feinstone ◽  
Deborah R. Taylor
Keyword(s):  
Endoplasmic Reticulum ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Er Stress ◽  
Envelope Protein ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Virus Envelope ◽  
Expression Levels ◽  
Virus Envelope Protein

ABSTRACT The hepatitis C virus envelope protein, E2, is an endoplasmic reticulum (ER)-bound protein that contains a region of sequence homology with the double-stranded RNA-activated protein kinase PKR and its substrate, the eukaryotic translation initiation factor 2 (eIF2). We previously reported that E2 modulates global translation through inhibition of the interferon-induced antiviral protein PKR through its PKR-eIF2α phosphorylation site homology domain (PePHD). Here we show that the PKR-like ER-resident kinase (PERK) binds to and is also inhibited by E2. At low expression levels, E2 induced ER stress, but at high expression levels, and in vitro, E2 inhibited PERK kinase activity. Mammalian cells that stably express E2 were refractory to the translation-inhibitory effects of ER stress inducers, and E2 relieved general translation inhibition induced by PERK. The PePHD of E2 was required for the rescue of translation that was inhibited by activated PERK, similar to our previous findings with PKR. Here we report the inhibition of a second eIF2α kinase by E2, and these results are consistent with a pseudosubstrate mechanism of inhibition of eIF2α kinases. These findings may also explain how the virus promotes persistent infection by overcoming the cellular ER stress 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.

scholarly journals The Lipid Droplet Binding Domain of Hepatitis C Virus Core Protein Is a Major Determinant for Efficient Virus Assembly

2007 ◽  
Vol 282 (51) ◽  
pp. 37158-37169 ◽  
Author(s):  
Anna Shavinskaya ◽  
Steeve Boulant ◽  
Francois Penin ◽  
John McLauchlan ◽  
Ralf Bartenschlager
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Lipid Droplet ◽  
Core Protein ◽  
Virus Assembly ◽  
Binding Domain ◽  
Major Determinant ◽  
Virus Core

scholarly journals Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virus-infected liver

2015 ◽  
Vol 21 (11) ◽  
pp. 3291-3299 ◽  
Author(s):  
Motoyuki Kohjima ◽  
Tsuyoshi Yoshimoto ◽  
Munechika Enjoji ◽  
Nobuyoshi Fukushima ◽  
Kunitaka Fukuizumi ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Pegylated Interferon ◽  
Expression Levels ◽  
Pegylated Interferon Plus Ribavirin ◽  
Infected Liver

scholarly journals rs62139665 Polymorphism in the Promoter Region of EpCAM Is Associated With Hepatitis C Virus-Related Hepatocellular Carcinoma Risk in Egyptians

2022 ◽  
Vol 11 ◽  
Author(s):  
Tarek Mohamed Kamal Motawi ◽  
Nermin Abdel Hamid Sadik ◽  
Dina Sabry ◽  
Sally Atef Fahim ◽  
Nancy Nabil Shahin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Protein Expression ◽  
Diagnostic Accuracy ◽  
Promoter Region ◽  
Stem Cell Marker ◽  
Expression Levels ◽  
Gene And Protein Expression ◽  
Epcam Gene

Hepatocellular carcinoma (HCC) is a universal health problem that is particularly alarming in Egypt. The major risk factor for HCC is hepatitis C virus (HCV) infection which is a main burden in Egypt. The epithelial cell adhesion molecule (EpCAM) is a stem cell marker involved in the tumorigenesis and progression of many malignancies, including HCC. We investigated the association of -935 C/G single nucleotide polymorphism in EpCAM promoter region (rs62139665) with HCC risk, EpCAM expression and overall survival in Egyptians. A total of 266 patients (128 HCV and 138 HCC cases) and 117 age- and sex-matched controls participated in this study. Genotyping, performed using allelic discrimination and confirmed by sequencing, revealed a significant association between EpCAM rs62139665 and HCC susceptibility, with higher GG genotype and G allele distribution in HCC patients than in non-HCC subjects. Such association was not detected in HCV patients compared to controls. EpCAM gene expression levels, determined in blood by RT-qPCR, and its serum protein expression levels, determined by ELISA, were significantly higher in GG relative to GC+CC genotype carriers in HCV and HCC patients in a recessive model. ROC analysis of EpCAM protein levels revealed significant discriminatory power between HCC patients and non-HCC subjects, with improved diagnostic accuracy when combining α-fetoprotein and EpCAM compared to that of α-fetoprotein alone. Altogether, EpCAM rs62139665 polymorphism is significantly associated with HCC and with EpCAM gene and protein expression levels in the Egyptian population. Moreover, serum EpCAM levels may hold promise for HCC diagnosis and for improving the diagnostic accuracy of α-fetoprotein.

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