scholarly journals Association of Hepatitis C Virus Replication with the Catecholamine Biosynthetic Pathway

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2139
Author(s):  
George Mpekoulis ◽  
Vassilina Tsopela ◽  
Georgios Panos ◽  
Vasileiοs Siozos ◽  
Katerina I. Kalliampakou ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Negative Relationship ◽  
Phosphatidylinositol 3 Kinase ◽  
Catecholamine Biosynthesis ◽  
Protein Levels ◽  
Negative Effect ◽  
Chemical Inhibition ◽  
Rate Limiting

A bidirectional negative relationship between Hepatitis C virus (HCV) replication and gene expression of the catecholamine biosynthetic enzyme L-Dopa decarboxylase (DDC) was previously shown in the liver and attributed at least to an association of DDC with phosphatidylinositol 3-kinase (PI3K). Here, we report that the biosynthesis and uptake of catecholamines restrict HCV replication in hepatocytes, while HCV has developed ways to reduce catecholamine production. By employing gene silencing, chemical inhibition or induction of the catecholamine biosynthetic and metabolic enzymes and transporters, and by applying the substrates or the products of the respective enzymes, we unravel the role of the different steps of the pathway in viral infection. We also provide evidence that the effect of catecholamines on HCV is strongly related with oxidative stress that is generated by their autoxidation in the cytosol, while antioxidants or treatments that lower cytosolic catecholamine levels positively affect the virus. To counteract the effect of catecholamines, HCV, apart from the already reported effects on DDC, causes the down-regulation of tyrosine hydroxylase that encodes the rate-limiting enzyme of catecholamine biosynthesis and suppresses dopamine beta-hydroxylase mRNA and protein amounts, while increasing the catecholamine degradation enzyme monoamine oxidase. Moreover, the NS4B viral protein is implicated in the effect of HCV on the ratio of the ~50 kDa DDC monomer and a ~120 kDa DDC complex, while the NS5A protein has a negative effect on total DDC protein levels.

scholarly journals Hepatitis C virus infection restricts human LINE-1 retrotransposition in hepatoma cells

2021 ◽  
Vol 17 (4) ◽  
pp. e1009496
Author(s):  
Anja Schöbel ◽  
Van Nguyen-Dinh ◽  
Gerald G. Schumann ◽  
Eva Herker
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Lipid Droplets ◽  
Viral Infections ◽  
Stress Granules ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Dependent Manner ◽  
Protein Levels ◽  
Negative Effect

LINE-1 (L1) retrotransposons are autonomous transposable elements that can affect gene expression and genome integrity. Potential consequences of exogenous viral infections for L1 activity have not been studied to date. Here, we report that hepatitis C virus (HCV) infection causes a significant increase of endogenous L1-encoded ORF1 protein (L1ORF1p) levels and translocation of L1ORF1p to HCV assembly sites at lipid droplets. HCV replication interferes with retrotransposition of engineered L1 reporter elements, which correlates with HCV RNA-induced formation of stress granules and can be partially rescued by knockdown of the stress granule protein G3BP1. Upon HCV infection, L1ORF1p localizes to stress granules, associates with HCV core in an RNA-dependent manner and translocates to lipid droplets. While HCV infection has a negative effect on L1 mobilization, L1ORF1p neither restricts nor promotes HCV infection. In summary, our data demonstrate that HCV infection causes an increase of endogenous L1 protein levels and that the observed restriction of retrotransposition of engineered L1 reporter elements is caused by sequestration of L1ORF1p in HCV-induced stress granules.

Role of autophagy in hepatitis C virus replication

2019 ◽  
Author(s):  
WI Twu ◽  
K Tabata ◽  
D Paul ◽  
R Bartenschlager
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Replication

Role of Hepatitis C Virus Core Antigen Assay in Blood Donors Screening at Zagazig University Hospitals

2018 ◽  
Vol 8 (1) ◽  
pp. 48-54
Author(s):  
Rashed Hassan ◽  
Abdelmonem Elshamy ◽  
Sameh Abdel Monem ◽  
Emad Moustafa ◽  
Essam Wahab
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Blood Donors ◽  
Core Antigen ◽  
University Hospitals ◽  
Virus Core ◽  
Antigen Assay

Hepatitis C virus‐associated indolent B‐cell lymphomas: A review on the role of the new direct antiviral agents therapy

2021 ◽  
Author(s):  
Cesare Mazzaro ◽  
Luigino Dal Maso ◽  
Marcella Visentini ◽  
Anna Ermacora ◽  
Pietro Andreone ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Agents ◽  
B Cell Lymphomas ◽  
Direct Antiviral Agents

scholarly journals Identification of Keratin 23 as a Hepatitis C Virus-Induced Host Factor in the Human Liver

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 610 ◽  
Author(s):  
Volker Kinast ◽  
Stefan L. Leber ◽  
Richard J. P. Brown ◽  
Gabrielle Vieyres ◽  
Patrick Behrendt ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
Ectopic Expression ◽  
Host Factor ◽  
Hcv Infection ◽  
Mrna Levels ◽  
Structural Support ◽  
Protein Levels ◽  
Inducible Protein

Keratin proteins form intermediate filaments, which provide structural support for many tissues. Multiple keratin family members are reported to be associated with the progression of liver disease of multiple etiologies. For example, keratin 23 (KRT23) was reported as a stress-inducible protein, whose expression levels correlate with the severity of liver disease. Hepatitis C virus (HCV) is a human pathogen that causes chronic liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma. However, a link between KRT23 and hepatitis C virus (HCV) infection has not been reported previously. In this study, we investigated KRT23 mRNA levels in datasets from liver biopsies of chronic hepatitis C (CHC) patients and in primary human hepatocytes experimentally infected with HCV, in addition to hepatoma cells. Interestingly, in each of these specimens, we observed an HCV-dependent increase of mRNA levels. Importantly, the KRT23 protein levels in patient plasma decreased upon viral clearance. Ectopic expression of KRT23 enhanced HCV infection; however, CRIPSPR/Cas9-mediated knockout did not show altered replication efficiency. Taken together, our study identifies KRT23 as a novel, virus-induced host-factor for hepatitis C virus.

Sign in / Sign up

Export Citation Format

Share Document