scholarly journals Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling

2019 ◽  
Vol 20 (6) ◽  
pp. 1321 ◽  
Author(s):  
Gesche Gerresheim ◽  
Jochen Bathke ◽  
Audrey Michel ◽  
Dmitri Andreev ◽  
Lyudmila Shalamova ◽  
...  

Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression—only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, and TRIB3) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes. Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming (“Warburg effect”) even in the hepatocellular carcinoma cells used here.

Author(s):  
Mohamed Hafez ◽  
Lina Jamil ◽  
Lubna Jamil ◽  
Sherine Ibrahim

IntroductionBackground: Hepatitis C is considered as one of the most popular diseases in Egypt. Our aim is to clarify the association between Cluster of Differentiation 24 (CD24) polymorphism, Talin-1 gene expression and the prevalence of hepatocellular carcinoma in Egyptian Hepatitis C virus patients.Material and methodsThe link between CD24 polymorphism rs8734 and the prevalence of hepatocellular carcinoma was assessed between 200 control subjects and 400 hepatitis C virus patients (HCV), patients were classified as follows; 200 patients with HCV and 200 with HCV and hepatocellular carcinoma (HCC) by histopathological assessment and PCR-restriction fragment length polymorphism (PCR-RFLP).ResultsResults: The hepatitis c patients with HCC showed significant increase in alpha fetoprotein (AFP) and Talin-1 gene expression compared to patients with HCV as well as in healthy volunteers. Furthermore, the frequencies of CD 24 170 CT/TT genotype were significantly higher in HCV patients without complications (60%) when compared to CC genotype (40%) (OR= 6 at X2= 14.41, P = 0.0007), and in HCV with HCC patients (90%) when compared to CC genotype (10%) (OR= 36 at X2= 14.41, P = 0.0007).ConclusionsThese data suggests that CD24 genetic polymorphism rs8734 and Talin-1 gene expression may be a significant determinant for the prevalence of hepatocellular carcinoma in HCV patients.


Viruses ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 591 ◽  
Author(s):  
Marie-Laure Plissonnier ◽  
Katharina Herzog ◽  
Massimo Levrero ◽  
Mirjam Zeisel

Hepatitis C virus (HCV) infection is a worldwide health problem and is one of the main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Despite recent improvements, effective treatments for HCC are still missing and new tools for early detection are needed. Non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression and key players in human carcinogenesis, including HCC. Aberrant expression of ncRNAs is associated with HCC metastasis, invasion, dissemination, and recurrence. This review will focus on the recent advances in ncRNA expression profiles, their dysregulation in HCV-related HCC, and the clinical perspective of ncRNA signatures for the early detection of HCC.


FEBS Letters ◽  
2003 ◽  
Vol 555 (3) ◽  
pp. 583-590 ◽  
Author(s):  
Toshimasa Okada ◽  
Norio Iizuka ◽  
Hisafumi Yamada-Okabe ◽  
Naohide Mori ◽  
Takao Tamesa ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Akihiro Tamori ◽  
Masaru Enomoto ◽  
Norifumi Kawada

Hepatitis C virus (HCV) infection is a major worldwide health problem. Chronic infection induces continuous inflammation in the liver, progression of hepatic fibrosis, eventual cirrhosis, and possible hepatocellular carcinoma. Eradication of the virus is one of the most important treatment aims. A number of promising new direct-acting antivirals (DAAs) have been developed over the past 10 years. Due to their increased efficacy, safety, and tolerability, interferon-free oral therapies with DAAs have been approved for patients with HCV, including those with cirrhosis. This review introduces the characteristics and results of recent clinical trials of several DAAs: NS3/4A protease inhibitors, NS5A inhibitors, and NS5B inhibitors. DAA treatment failure and prognosis after DAA therapy are also discussed.


2018 ◽  
Vol 12 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Ivan Schietroma ◽  
Giuseppe Corano Scheri ◽  
Claudia Pinacchio ◽  
Maura Statzu ◽  
Arnolfo Petruzziello ◽  
...  

Introduction:Globally, between 64 and 103 million people are chronically infected with Hepatitis C virus (HCV), with more than 4.6 million people in the United States and is associated with more than 15.000 deaths annually. Chronic infection can result in cirrhosis and hepatocellular carcinoma.Explanation:Epidemiological studies have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC), mainly through chronic inflammation, cell deaths, and proliferation. Despite the new direct-acting antiviral drugs (DAA’s) being able to clear the HCV, HCC recurrence rate in these patients is still observed.Conclusion:In this review we highlighted some aspects that could be involved in the onset of HCV-induced HCC such as immune system, viral factors and host genetics factors.Moreover, we focused on some of the last reports about the effects of DAA’s on the HCV clearance and their potential implications in HCC recurrence.


Sign in / Sign up

Export Citation Format

Share Document