REVIEW
Recent advances in the anti-HCV mechanisms of interferon

https://doi.org/10.1016/j.apsb.2014.06.010Get rights and content
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Abstract

Interferon (IFN) in combination with ribavirin has been the standard of care (SOC) for chronic hepatitis C for the past few decades. Although the current SOC lacks the desired efficacy, and 4 new direct-acting antiviral agents have been recently approved, interferons are still likely to remain the cornerstone of therapy for some time. Moreover, as an important cytokine system of innate immunity, host interferon signaling provides a powerful antiviral response. Nevertheless, the mechanisms by which HCV infection controls interferon production, and how interferons, in turn, trigger anti-HCV activities as well as control the outcome of HCV infection remain to be clarified. In this report, we review current progress in understanding the mechanisms of IFN against HCV, and also summarize the knowledge of induction of interferon signaling by HCV infection.

Graphical abstract

This review summarized pathways of interferon induction and regulation by HCV infection, and how interferon in turn triggers anti-HCV activities as well as control the outcome of HCV infection.

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Key words

Interferon
Hepatitis C virus
Antiviral agent
Molecular mechanism

Abbreviations

CHC
chronic hepatitis C
DCs
dendritic cells
DNAM1
DNAX accessory molecule-1
dsRNA
double-stranded RNA
E2
envelop 2
GAS
IFN-γ-activated site
GWAS
genome-wide association studies
IFN
interferon
IFN-α
interferon-α
IFNAR1
interferon-alpha receptor 1
IFNAR2
interferon-alpha receptor 2
IFNGR1
interferon gamma receptor 1
IFNGR2
interferon gamma receptor 2
IFNL4
IFN-lambda 4
IL-10R2
interleukin-10 receptor 2
IL-29
interleukin-29
IRF-3
interferon regulatory factor 3
IRGs
IFN regulatory genes
ISG15
interferon-stimulated gene 15
ISGs
IFN-stimulated genes
ISGF3
IFN-stimulated gene factor 3
ISREs
IFN-stimulated response elements
JAKs
Janus activated kinases
MAVS
mitochondrial antiviral signaling protein
MDA-5
melanoma differentiation-associated gene-5
MHC
major histocompatibility complex
NKCs
natural killer cells
NKTCs
natural killer T cells
OAS
2′-5′-oligoadenylate synthetase
PAMPs
pathogen-associated molecular patterns
PBMCs
peripheral blood mononuclear cells
pDC
plasmacytoid dendritic cell
PKR
protein kinase R
PRRs
pattern recognition receptors
RdRp
RNA dependent RNA polymerase
RIG-I
retinoic acid-inducible gene-I
RLRs
RIG-I-like receptors
SNPs
single-nucleotide polymorphisms
SOC
standard of care
STAT1
signal transducer and activator of transcription 1
STAT2
signal transducer and activator of transcription 2
SVR
sustained virological response
TH1
T-helper-1
TH2
T-helper-2
TLRs
Toll-like receptors
TYK2
tyrosine kinase 2
USP18
ubiquitin specific peptidase 18

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Peer review under responsibility of Institute of Materia Medica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association.

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