Ovarian tumor domain-containing protease-1 gene inhibits the antiviral effects of IFN-α
10.3760/cma.j.cn112309-20231006-00092
- VernacularTitle:卵巢癌结构域蛋白酶-1基因拮抗IFN-α抗病毒效应研究
- Author:
Minghui ZHOU
1
;
Yanjun JIANG
;
Shuyi SONG
;
Yuan HU
Author Information
1. 重庆医科大学感染性疾病分子生物学教育部重点实验室，重庆 400016
- Keywords:
Ovarian cancer domain containing protease-1 (OTUD1);
IFN-α;
JAK-STAT signaling pathway;
Antiviral effect
- From:
Chinese Journal of Microbiology and Immunology
2024;44(5):382-389
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of ovarian cancer domain containing protease-1 (OTUD1) gene on the typeⅠ interferon signaling pathway, and its impact on the antiviral effects of IFN-α.Methods:Dual-luciferase reporter assay was performed to detect the effects of OTUD1 gene on the transcriptional activity of interferon-stimulated response element (ISRE) promoter. Quantitative real-time PCR (qPCR) was used to detect the effects of OTUD1 on IFN-α-induced expression of interferon-stimulated genes (ISGs). The effects of OTUD1 gene on the expression of key proteins in the IFN-α signal transduction pathway were analyzed by Western blot, and its effects on IFN-α-mediated inhibition of hepatitis B virus replication were detected by qPCR and ELISA.Results:In HEK293T and Huh7.0 cells, OTUD1 down-regulated the transcriptional activity of ISRE promoter in the interferon signaling pathway and the expression of antiviral genes such as ISG15 and ISG56. In HEK293T cells, OTUD1 reduced the expression of phospho-Jak1 (p-JAK1) at protein level, but the catalytic inactive mutant of OTUD1 (C320S) could not regulate the expression of ISGs or p-JAK1. In Huh7.0 cells, OTUD1 antagonized the inhibitory effect of IFN-α on hepatitis B virus replication.Conclusions:OTUD1 with the ubiquitination activity can inhibit the interferon JAK-STAT signaling pathway and the expression of ISGs by down-regulating the expression of p-JAK1 protein. OTUD1 antagonizes the effect of IFN-α on viral replication and that may be related to the interferon-induced JAK-STAT signaling pathway.
