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Virology Journal
Published in: Virology Journal 1/2023

Open Access 01-12-2023 | Influenza | Research

ARIH1 inhibits influenza A virus replication and facilitates RIG-I dependent immune signaling by interacting with SQSTM1/p62

Authors: Shengyu Wang, Zhenrong Li, Yaping Chen, Sanli Gao, Junhua Qiao, Haoru Liu, Hong Song, Dishu Ao, Xin Sun

Published in: Virology Journal | Issue 1/2023

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Abstract

Background

Multiple host factors are involved in modulating type I interferon expression induced by viruses; however, the mechanism is not fully elucidated. Influenza A virus infection causes severe respiratory symptoms and triggers a series of signaling cascades and host innate immune responses, including interferon production. The co-IP/MS technology was used to screen several antiviral factors in the early stage. Among these factors, ariadne-1 homolog (ARIH1) caught our attention.

Methods

Western blot assay was performed to detect the level of proteins and software ImageJ was used to analyze the band intensities. Polymerase activity assay was conducted to evaluate the polymerase activity of influenza A virus. Tissue culture infective dose (TCID50) assay was performed to measure influenza A virus titers, and quantitative RT-PCR assay was applied to test the mRNA level of IFN-β, ISG56, and CXCL10. Luciferase reporter assay was used to confirm the target of ARIH1 in RIG-I signaling. Immunoprecipitation assay was performed to detect the interaction and the ubiquitination of the proteins. All data were analyzed by biostatistical methods and presented as means ± standard deviation from three independent experiments. Statistical significance was determined using two-tailed student’s t test. A P value of less than 0.05 was considered statistically significant, and a P value of less than 0.01 was considered highly significant (ns, P ≥ 0.05; *, P < 0.05; and **, P < 0.01).

Results

We found that ARIH1, a member of E3 ubiquitin ligases, enhanced cellular antiviral responses. Subsequent study showed that ARIH1 was up-regulated during influenza A virus infection. Further analysis showed that ARIH1 enhanced IFN-β and downstream gene expression by affecting the degradation of RIG-I through the SQSTM1/p62 signaling pathway.

Conclusion

This newly revealed mechanism shows that cellular response increases of ARIH1 and promotes IFN-β expression to boost host survival during viral infection.
Appendix
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Metadata
Title
ARIH1 inhibits influenza A virus replication and facilitates RIG-I dependent immune signaling by interacting with SQSTM1/p62
Authors
Shengyu Wang
Zhenrong Li
Yaping Chen
Sanli Gao
Junhua Qiao
Haoru Liu
Hong Song
Dishu Ao
Xin Sun
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2023
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-023-02022-1

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