Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice
| العنوان: | Macrophage scavenger receptor 1 controls Chikungunya virus infection through autophagy in mice |
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| المؤلفون: | Leilei Wang, Duomeng Yang, Tingting Geng, Jesse Hwang, Penghua Wang, Long Yang, Shu Zhu, Harshada Ketkar, Fuping You, Tao Lin, Richard A. Flavell, Erol Fikrig, Jinzhu Ma, Gong Cheng, Jianfeng Dai, Guang Yang, Anthony T. Vella, Yanlin Wang |
| المصدر: | Communications Biology Communications Biology, Vol 3, Iss 1, Pp 1-11 (2020) |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, viruses, Alphaviruses, Medicine (miscellaneous), Alphavirus, Biology, General Biochemistry, Genetics and Molecular Biology, Virus, Article, MSR1, ATG12, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, CRISPR-Associated Protein 9, Autophagy, Animals, Humans, lcsh:QH301-705.5, ATG16L1, Innate immunity, Gene Editing, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, virus diseases, Scavenger Receptors, Class A, biology.organism_classification, Virology, Mice, Inbred C57BL, 030104 developmental biology, HEK293 Cells, lcsh:Biology (General), Viral infection, Knockout mouse, Chikungunya Fever, CRISPR-Cas Systems, General Agricultural and Biological Sciences, Chikungunya virus, 030215 immunology |
| الوصف: | 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. Using Msr1 knockout mice, Long Yang et al. demonstrate that macrophage scavenger receptor 1 (MSR1) activates autophagy to restrict the proliferation of Chikungunya virus, an alphavirus that causes crippling joint stiffness. This study provides insights into how host cellular machinery fights off Chikungunya virus. |
| اللغة: | English |
| تدمد: | 2399-3642 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84cc5064c73bd7595646b2ccb1103931Test http://europepmc.org/articles/PMC7545163Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....84cc5064c73bd7595646b2ccb1103931 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23993642 |
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