NYMC Faculty Publications
Macrophage Scavenger Receptor 1 Controls Chikungunya Virus Infection through Autophagy in Mice
DOI
10.1038/s42003-020-01285-6
Journal Title
Communications Biology
First Page
556
Last Page
556
Document Type
Article
Publication Date
10-8-2020
Department
Pathology, Microbiology and Immunology
Abstract
Macrophage scavenger receptor 1 (MSR1) mediates the endocytosis of modified low-density lipoproteins and plays an important antiviral role. However, the molecular mechanism underlying MSR1 antiviral actions remains elusive. We report that MSR1 activates autophagy to restrict infection of Chikungunya virus (CHIKV), an arthritogenic alphavirus that causes acute and chronic crippling arthralgia. Msr1 expression was rapidly upregulated after CHIKV infection in mice. Msr1 knockout mice had elevated viral loads and increased susceptibility to CHIKV arthritis along with a normal type I IFN response. Induction of LC3 lipidation by CHIKV, a marker of autophagy, was reduced in Msr1-/- cells. Mechanistically, MSR1 interacted with ATG12 through its cytoplasmic tail and this interaction was enhanced by CHIKV nsP1 protein. MSR1 repressed CHIKV replication through ATG5-ATG12-ATG16L1 and this was dependent on the FIP200-and-WIPI2-binding domain, but not the WD40 domain of ATG16L1. Our results elucidate an antiviral role for MSR1 involving the autophagic function of ATG5-ATG12-ATG16L1.
Recommended Citation
Yang, L., Geng, T., Yang, G., Ma, J., Wang, L., Ketkar, H., Yang, D., Lin, T., Hwang, J., Zhu, S., Wang, Y., Dai, J., You, F., Cheng, G., Vella, A. T., Flavell, R. A., Fikrig, E., & Wang, P. (2020). Macrophage Scavenger Receptor 1 Controls Chikungunya Virus Infection through Autophagy in Mice. Communications Biology, 3 (1), 556-556. https://doi.org/10.1038/s42003-020-01285-6
