puc-header

The STING-MSR1 Axis Controls RNA Virus Infection Through Noncanonical Autophagy

73 Pages Posted: 5 Mar 2019 Publication Status: Review Complete

See all articles by Long Yang

Long Yang

New York Medical College - Department of Microbiology and Immunology

Guang Yang

New York Medical College - Department of Microbiology and Immunology; Jinan University - Department of Parasitology

Tingting Geng

University of Connecticut - Department of Immunology

Jinzhu Ma

New York Medical College - Department of Microbiology and Immunology

Leilei Wang

New York Medical College - Department of Microbiology and Immunology

Harshada Ketkhar

New York Medical College - Department of Microbiology and Immunology

Tao Lin

Jinan University - Department of Parasitology

Yujiao Zhao

New York Medical College - Department of Microbiology and Immunology

Jesse Hwang

Yale University - Section of Infectious Diseases

Zhenlong Liu

McGill University - Lady Davis Institute for Medical Research

Dana Mordue

New York Medical College - Department of Microbiology and Immunology

Yanlin Wang

University of Connecticut - Department of Medicine

Shu Zhu

University of Science and Technology of China (USTC) - School of Life Sciences

Jianfeng Dai

Soochow University - Institute of Biology and Medical Sciences

Fuping You

Peking University - School of Basic Medical Sciences

Antony Vella

University of Connecticut - Department of Immunology

Gong Cheng

Tsinghua University - Department of Basic Sciences

Rongtuan Lin

McGill University - Lady Davis Institute for Medical Research

Richard A. Flavell

Yale University - Department of Immunobiology

Erol Fikrig

Yale University - Section of Infectious Diseases; Howard Hughes Medical Institute (HHMI) - Chevy Chase

Penghua Wang

University of Connecticut - Department of Immunology; New York Medical College - Department of Microbiology and Immunology

More...

Abstract

The stimulator-of-interferon-gene (STING) pathway controls both DNA and RNA virus infection. STING is critical for induction of type I interferons (IFN-I) during DNA virus infection, while the molecular mechanism underlying the anti-RNA virus function of STING remains largely elusive. We show that the STING signaling pathway regulates expression of macrophage scavenger receptor 1 (MSR1), which activates a cell-intrinsic antiviral mechanism through autophagy related ATG5-ATG12. Mice deficient in Sting or Msr1 had increased viral replication and susceptibility to Chikungunya virus (CHIKV)-induced arthritis. Repression of CHIKV replication by MSR1 was dependent on ATG5-ATG12, but independent of other autophagy components such as ULK1 and Beclin 1. MSR1 interacted with ATG5–ATG12 following CHIKV infection, and this interaction was independent of canonical autophagy. Induction of MSR1 expression by CHIKV was partially dependent on the STING signaling. Our results elucidate an antiviral role of the STING-MSR1 axis involving the non-canonical autophagy-related function of ATG5-ATG12.

Keywords: STING, macrophage scavenger receptor, MSR1, Chikungunya virus, autophagy

Suggested Citation

Yang, Long and Yang, Guang and Geng, Tingting and Ma, Jinzhu and Wang, Leilei and Ketkhar, Harshada and Lin, Tao and Zhao, Yujiao and Hwang, Jesse and Liu, Zhenlong and Mordue, Dana and Wang, Yanlin and Zhu, Shu and Dai, Jianfeng and You, Fuping and Vella, Antony and Cheng, Gong and Lin, Rongtuan and Flavell, Richard A. and Fikrig, Erol and Wang, Penghua, The STING-MSR1 Axis Controls RNA Virus Infection Through Noncanonical Autophagy (March 5, 2019). Available at SSRN: https://ssrn.com/abstract=3346986 or http://dx.doi.org/10.2139/ssrn.3346986
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Long Yang

New York Medical College - Department of Microbiology and Immunology

Valhalla, NY 10595
United States

Guang Yang

New York Medical College - Department of Microbiology and Immunology

Valhalla, NY 10595
United States

Jinan University - Department of Parasitology

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Tingting Geng

University of Connecticut - Department of Immunology

263 Farmington Ave.
Farmington, CT 06030-2103
United States

Jinzhu Ma

New York Medical College - Department of Microbiology and Immunology

Valhalla, NY 10595
United States

Leilei Wang

New York Medical College - Department of Microbiology and Immunology

Valhalla, NY 10595
United States

Harshada Ketkhar

New York Medical College - Department of Microbiology and Immunology

Valhalla, NY 10595
United States

Tao Lin

Jinan University - Department of Parasitology

Huang Pu Da Dao Xi 601, Tian He District
Guangzhou, Guangdong 510632
China

Yujiao Zhao

New York Medical College - Department of Microbiology and Immunology

Valhalla, NY 10595
United States

Jesse Hwang

Yale University - Section of Infectious Diseases

New Haven, CT 06520
United States

Zhenlong Liu

McGill University - Lady Davis Institute for Medical Research

5750 Côte-des-Neiges Rd
Montreal, QC H3S 1Y9
Canada

Dana Mordue

New York Medical College - Department of Microbiology and Immunology

Valhalla, NY 10595
United States

Yanlin Wang

University of Connecticut - Department of Medicine

Storrs, CT 06269-1063
United States

Shu Zhu

University of Science and Technology of China (USTC) - School of Life Sciences

96, Jinzhai Road
Hefei, Anhui 230026
China

Jianfeng Dai

Soochow University - Institute of Biology and Medical Sciences

No. 1 Shizi Street
Taipei, Jiangsu 215006
Taiwan

Fuping You

Peking University - School of Basic Medical Sciences

China

Antony Vella

University of Connecticut - Department of Immunology

263 Farmington Ave.
Farmington, CT 06030-2103
United States

Gong Cheng

Tsinghua University - Department of Basic Sciences

Beijing, 100084
China

Rongtuan Lin

McGill University - Lady Davis Institute for Medical Research

5750 Côte-des-Neiges Rd
Montreal, QC H3S 1Y9
Canada

Richard A. Flavell

Yale University - Department of Immunobiology ( email )

300 Cedar Street
New Haven, CT 06520
United States

Erol Fikrig

Yale University - Section of Infectious Diseases ( email )

New Haven, CT 06520
United States

Howard Hughes Medical Institute (HHMI) - Chevy Chase ( email )

4000 Jones Bridge Road
Chevy Chase, MD 20815-6789
United States

Penghua Wang (Contact Author)

University of Connecticut - Department of Immunology ( email )

263 Farmington Ave.
Farmington, CT 06030-2103
United States

New York Medical College - Department of Microbiology and Immunology ( email )

Valhalla, NY 10595
United States

Click here to go to Cell.com

Paper statistics

Abstract Views
768
Downloads
24