Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway

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Serval ID
serval:BIB_02A3D2F9E1B5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway
Journal
Journal of General Virology
Author(s)
Frese  M., Pietschmann  T., Moradpour  D., Haller  O., Bartenschlager  R.
ISSN
0022-1317 (Print)
Publication state
Published
Issued date
04/2001
Volume
82
Number
Pt 4
Pages
723-33
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Apr
Abstract
Hepatitis C virus (HCV) persists in the majority of infected individuals and is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is currently treated with interferon (IFN)-alpha or with a combination of IFN-alpha and ribavirin. The availability of an HCV replicon system (Lohmann et al., SCIENCE: 285, 110-113, 1999) allowed the investigation of the effects of IFN on genuine HCV replication in cultured cells. It is shown here that IFN-alpha inhibits subgenomic HCV RNA replication in HuH-7 human hepatoma cells. Immunofluorescence, Western blot and Northern blot analysis revealed that levels of both HCV protein and replicon RNA were reduced after treatment with IFN-alpha in a dose-dependent manner. In further experiments, it was investigated whether MxA plays a role in the inhibition of HCV. The human MxA protein is an IFN-induced GTPase that has antiviral activity against various RNA viruses. However, HCV RNA replication was not affected in transfected HuH-7 cells that transiently overexpressed MxA. Moreover, a dominant-negative mutant of MxA did not interfere with the antiviral activity of IFN-alpha against HCV RNA replication. Taken together, these results demonstrate that IFN-alpha inhibits HCV replicons via an MxA-independent pathway.
Keywords
Antiviral Agents/*pharmacology/*physiology Dose-Response Relationship, Drug *GTP-Binding Proteins Hepacivirus/*drug effects/genetics Humans Interferon-alpha/*pharmacology Proteins/*physiology RNA, Viral/*biosynthesis Replicon Tumor Cells, Cultured Viral Nonstructural Proteins/physiology
Pubmed
Web of science
Create date
25/01/2008 16:05
Last modification date
20/08/2019 12:24
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