Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling

Lin Li; Qing-Song Lei; Shu-Jun Zhang; Ling-Na Kong; Bo Qin

doi:10.1371/journal.pone.0156496

Suppression of USP18 Potentiates the Anti-HBV Activity of Interferon Alpha in HepG2.2.15 Cells via JAK/STAT Signaling

PLoS One. 2016 May 26;11(5):e0156496. doi: 10.1371/journal.pone.0156496. eCollection 2016.

Authors

Lin Li¹, Qing-Song Lei¹, Shu-Jun Zhang¹, Ling-Na Kong^{1

2}, Bo Qin¹

Affiliations

¹ Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
² The Nursing College of Chongqing Medical University, Chongqing, 400016, P.R. China.

Abstract

Ubiquitin-specific protease 18 (USP18, also known as UBP43) has both interferon stimulated gene 15 (ISG15) dependent and ISG15-independent functions. By silencing the expression of USP18 in HepG2.2.15 cells, we studied the effect of USP18 on the anti-HBV activity of IFN-F and demonstrated that knockdown of USP18 significantly Inhibited the HBV expression and increased the expression of ISGs. Levels of hepatitis B virus surface antigen (HBsAg), hepatitis B virus e antigen (HBeAg), HBV DNA and intracellular hepatitis B virus core antigen (HBcAg) were dramatically decreased with or without treatment of indicated dose of IFN-F. Suppression of USP18 activated the JAK/STAT signaling pathway as shown by the increased and prolonged expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) in combination with enhanced expression of several interferon stimulated genes (ISGs). Our results indicated that USP18 modulates the anti-HBV activity of IFN-F via activation of the JAK/STAT signaling pathway in Hepg2.2.15 cells.

MeSH terms

DNA, Viral / immunology
Endopeptidases / immunology*
Gene Expression Regulation / drug effects*
Gene Expression Regulation / immunology
Gene Expression Regulation, Viral / drug effects
Gene Expression Regulation, Viral / immunology
Hep G2 Cells
Hepatitis B / drug therapy
Hepatitis B / immunology*
Hepatitis B Surface Antigens / immunology
Hepatitis B e Antigens / immunology
Hepatitis B virus / immunology*
Humans
Interferon-alpha / pharmacology*
Janus Kinases / immunology*
STAT1 Transcription Factor / immunology*
Signal Transduction / drug effects*
Signal Transduction / immunology
Ubiquitin Thiolesterase

Substances

DNA, Viral
Hepatitis B Surface Antigens
Hepatitis B e Antigens
Interferon-alpha
STAT1 Transcription Factor
STAT1 protein, human
Janus Kinases
Endopeptidases
USP18 protein, human
Ubiquitin Thiolesterase

Grants and funding

This study was supported by grants (81271838) from the National Science Foundation of China, http://www.nsfc.gov.cn. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.