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© 2018. This work is published under http://creativecommons.org/licenses/by-nc/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background/Aims

Hepatitis C virus (HCV) replicates in the peripheral blood mononuclear cells (PBMCs), leading to the production of type I interferons (IFNs). It is well known that the gene expression profile of PBMC is similar to that of the liver. The present study explored the dynamic gene expression profile of PBMCs collected from HCV-infected patients undergoing direct-acting antiviral (DAA) therapy.

Methods

A prospective cohort comprising 27 patients under DAA therapy was formed. Expression level of IFN-β and its downstream interferon-stimulated genes (ISGs) was measured in PBMCs before and after DAA treatment. Furthermore, immunoblotting was performed to identify the signaling molecules involved in the expression of ISGs.

Results

The pretreatment expression level of interferon-induced protein 44 (IFI44) and C-X-C motif chemokine ligand 10 (CXCL10) correlated with the pretreatment expression level of IFN-β. After DAA treatment, a significant decrease in the expression levels of IFN-β, IFI44, and CXCL10 was observed in the PBMCs. Furthermore, the pretreatment expression level of IFN-β and ISGs correlated with the level of signal transducer and activator of transcription 1 (STAT1) phosphorylation, and DAA treatment abrogated STAT1 phosphorylation.

Conclusions

Pretreatment activation of IFN-β response is rapidly normalized after DAA treatment. The present study suggests that the decreased type I IFN response by the clearance of HCV might contribute to DAA-induced alleviation of extrahepatic manifestation of chronic HCV infection.

Details

Title
Interferon-free treatment for hepatitis C virus infection induces normalization of extrahepatic type I interferon signaling
Author
Sung, Pil Soo; Lee, Eun Byul; Park, Dong Jun; Lozada, Angelo; Jang, Jeong Won; Bae, Si Hyun; Jong Young Choi; Seung Kew Yoon  VIAFID ORCID Logo 
Pages
302-310
Section
Original Article
Publication year
2018
Publication date
Sep 2018
Publisher
Korean Association for the Study of the Liver
ISSN
22872728
e-ISSN
2287285X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3125556265
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by-nc/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.