Mitochondrial C11orf83 is a potent Antiviral Protein Independent of interferon production

Yun Yang; Shaoquan Xiong; Bei Cai; Hui Luo; E Dong; Qiqi Li; Gaili Ji; Chengjian Zhao; Yanjun Wen; Yuquan Wei; Hanshuo Yang

doi:10.1038/srep44303

Mitochondrial C11orf83 is a potent Antiviral Protein Independent of interferon production

Sci Rep. 2017 Apr 18:7:44303. doi: 10.1038/srep44303.

Authors

Yun Yang¹, Shaoquan Xiong^{1

2}, Bei Cai³, Hui Luo¹, E Dong¹, Qiqi Li¹, Gaili Ji¹, Chengjian Zhao¹, Yanjun Wen¹, Yuquan Wei¹, Hanshuo Yang¹

Affiliations

¹ State Key Laboratory of Biotherapy and Cancer center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China.
² Department of Oncology, Affilicated Hospital of ChengDu University of Traditional Chinese Medicine, 610041, Chengdu, China.
³ Department of Laboratory Medicine/Research Center of Clinical Laboratory Medicine, West China Hospital, Sichuan University, 610041, Chengdu, China.

Abstract

Mitochondria have a central position in innate immune response via the adaptor protein MAVS in mitochondrial outer membrane to limit viral replication by inducing interferon production. Here, we reported that C11orf83, a component of complex III of electronic transfer chain in mitochondrial inner membrane, was a potent antiviral protein independent of interferon production. C11orf83 expression significantly increased in response to viral infection, and endows cells with stronger capability of inhibiting viral replication. Deletion of C11orf83 permits viral replication easier and cells were more vulnerable to viral killing. These effects mainly were mediated by triggering OAS3-RNase L system. C11orf83 overexpression induced higher transcription of OAS3, and knockdown either OAS3 or RNase L impaired the antiviral capability of C11orf83. Interestingly, the signaling from C11orf83 to OAS3-RNase L was independent of interferon production. Thus, our findings suggested a new antiviral mechanism by bridging cell metabolic machinery component with antiviral effectors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

2',5'-Oligoadenylate Synthetase / genetics
2',5'-Oligoadenylate Synthetase / immunology*
Animals
CRISPR-Cas Systems
Carrier Proteins / genetics
Carrier Proteins / immunology*
Chlorocebus aethiops
Endoribonucleases / genetics
Endoribonucleases / immunology*
Gene Deletion
Gene Expression Regulation
Genes, Reporter
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
HEK293 Cells
Hep G2 Cells
Host-Pathogen Interactions*
Human Umbilical Vein Endothelial Cells
Humans
Immunity, Innate
Interferon-gamma / genetics
Interferon-gamma / immunology
Luciferases / genetics
Luciferases / metabolism
Mitochondria / genetics
Mitochondria / immunology*
Signal Transduction
Vero Cells
Vesicular stomatitis Indiana virus / genetics
Vesicular stomatitis Indiana virus / immunology*
Virus Replication

Substances

Carrier Proteins
UQCC3 protein, human
enhanced green fluorescent protein
Green Fluorescent Proteins
Interferon-gamma
Luciferases
2',5'-Oligoadenylate Synthetase
OAS3 protein, human
Endoribonucleases
2-5A-dependent ribonuclease