scholarly journals Repression of Interferon Regulatory Factor 1 by Hepatitis C Virus Core Protein Results in Inhibition of Antiviral and Immunomodulatory Genes

2006 ◽  
Vol 81 (1) ◽  
pp. 202-214 ◽  
Author(s):  
Anna R. Ciccaglione ◽  
Emilia Stellacci ◽  
Cinzia Marcantonio ◽  
Valentina Muto ◽  
Michele Equestre ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Interferon Regulatory Factor ◽  
Structural Proteins ◽  
Transcriptional Level ◽  
Structural Protein ◽  
Regulatory Factor ◽  
The Core ◽  
Interferon Regulatory Factor 1

ABSTRACT Hepatitis C virus (HCV) proteins are known to interfere at several levels with both innate and adaptive responses of the host. A key target in these effects is the interferon (IFN) signaling pathway. While the effects of nonstructural proteins are well established, the role of structural proteins remains controversial. We investigated the effect of HCV structural proteins on the expression of interferon regulatory factor 1 (IRF-1), a secondary transcription factor of the IFN system responsible for inducing several key antiviral and immunomodulatory genes. We found substantial inhibition of IRF-1 expression in cells expressing the entire HCV replicon. Suppression of IRF-1 synthesis was mainly mediated by the core structural protein and occurred at the transcriptional level. The core protein in turn exerted a transcriptional repression of several interferon-stimulated genes, targets of IRF-1, including interleukin-15 (IL-15), IL-12, and low-molecular-mass polypeptide 2. These data recapitulate in a unifying mechanism, i.e., repression of IRF-1 expression, many previously described pathogenetic effects of HCV core protein and suggest that HCV core-induced IRF-1 repression may play a pivotal role in establishing persistent infection by dampening an effective immune response.

Interferon regulatory factor-1 promoter polymorphism and the outcome of hepatitis C virus infection

2006 ◽  
Vol 18 (9) ◽  
pp. 991-997 ◽  
Author(s):  
Perdita Wietzke-Braun ◽  
Adil B. Maouzi ◽  
Larissa B. M??nhardt ◽  
Heike Bickeb??ller ◽  
Giuliano Ramadori ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Interferon Regulatory Factor ◽  
Promoter Polymorphism ◽  
Hepatitis C Virus Infection ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 1

scholarly journals Regulation of Hepatitis C Virus Replication by Interferon Regulatory Factor 1

2004 ◽  
Vol 78 (18) ◽  
pp. 9713-9720 ◽  
Author(s):  
Nobuhiko Kanazawa ◽  
Masayuki Kurosaki ◽  
Naoya Sakamoto ◽  
Nobuyuki Enomoto ◽  
Yasuhiro Itsui ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Interferon Regulatory Factor ◽  
Luciferase Reporter ◽  
Regulatory Factor ◽  
Antiviral Responses ◽  
Baseline Activity ◽  
Interferon Regulatory Factor 1 ◽  
Huh7 Cells ◽  
In Cells

ABSTRACT Cellular antiviral responses are mediated partly by the expression of interferon-stimulated genes, triggered by viral genomes, their transcripts and replicative intermediates. Persistent replication of a hepatitis C virus (HCV) replicon suggests that the replicon does not elicit cellular innate antiviral responses. In the present study, we investigated regulatory factors of the interferon-mediated antiviral system in cells expressing an HCV replicon. Luciferase reporter assays revealed that the baseline activity of the interferon-stimulated response element (ISRE) was significantly lower in cells harboring the replicon than in naive cells. Among the proteins involved in the IFN/Jak/STAT pathway and in ISRE activity, the expression level of interferon regulatory factor 1 (IRF-1) was found to be significantly lower in cells harboring the replicon. Transfection of an IRF-1 expression construct into cells harboring the replicon caused an increase of ISRE activity, accompanied by suppression of expression of the HCV replicon. Moreover, in cured Huh7 cells from which the HCV replicon had been eliminated, the expression levels of IRF-1 and ISRE activity also were suppressed, demonstrating that the decrease of IRF-1 is attributable, not to active suppression by the viral proteins, but to adaptation of cells that enables replication of the HCV subgenome. The high permissiveness of the cured cells for the replicon was abolished by transgenic supplementation of IRF-1 expression. Taken together, IRF-1 is one of the key host factors that regulate intracellular HCV replication through modulation of interferon-stimulated-gene-mediated antiviral responses.

608 Regulation of intracellular hepatitis C virus replication by interferon regulatory factor-1

Hepatology ◽  
2003 ◽  
Vol 38 ◽  
pp. 455-455
Author(s):  
N KANAZAWA ◽  
M KUROSAKI ◽  
N SAKAMOTO ◽  
N ENOMOTO ◽  
T YAMASHIRO ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Replication ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 1

scholarly journals Impairment of interferon regulatory factor-3 activation by hepatitis C virus core protein basic amino acid region 1

2012 ◽  
Vol 428 (4) ◽  
pp. 494-499 ◽  
Author(s):  
Kazuaki Inoue ◽  
Kyoko Tsukiyama-Kohara ◽  
Chiho Matsuda ◽  
Mitsutoshi Yoneyama ◽  
Takashi Fujita ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Amino Acid ◽  
Core Protein ◽  
Basic Amino Acid ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Amino Acid Region ◽  
Virus Core ◽  
Acid Region

Interfering with hepatitis C virus assembly in vitro using affinity peptides directed towards core protein

2012 ◽  
Vol 58 (4) ◽  
pp. 475-482
Author(s):  
Jean-Baptiste Duvignaud ◽  
Nathalie Majeau ◽  
Priscilla Delisle ◽  
Normand Voyer ◽  
Stéphane M. Gagné ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Self Assembly ◽  
Core Protein ◽  
Virus Assembly ◽  
Viral Assembly ◽  
Structural Protein ◽  
Ns5a Protein ◽  
The Core

Viral assembly is a crucial key step in the life cycle of every virus. In the case of Hepatitis C virus (HCV), the core protein is the only structural protein to interact directly with the viral genomic RNA. Purified recombinant core protein is able to self-assemble in vitro into nucleocapsid-like particles upon addition of a structured RNA, providing a robust assay with which to study HCV assembly. Inhibition of self-assembly of the C170 core protein (first 170 amino acids) was tested using short peptides derived from the HCV core, from HCV NS5A protein, and from diverse proteins (p21 and p73) known to interact with HCV core protein. Interestingly, peptides derived from the core were the best inhibitors. These peptides are derived from regions of the core predicted to be involved in the interaction between core subunits during viral assembly. We also demonstrated that a peptide derived from the C-terminal end of NS5A protein moderately inhibits the assembly process.

Sign in / Sign up

Export Citation Format

Share Document