A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencing
Abstract Background Neurotropic virus infection can cause serious damage to the central nervous system (CNS) in both humans and animals. The complexity of the CNS poses unique challenges to investigate the infection of these viruses in the brain using traditional techniques. Methods In this study, w...
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Language: | English |
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Wiley
2022-01-01
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Series: | Clinical and Translational Medicine |
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Online Access: | https://doi.org/10.1002/ctm2.700 |
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author | Yachun Zhang Xudong Xing Ben Long Yandi Cao Simeng Hu Xiangning Li Yalan Yu Dayong Tian Baokun Sui Zhaochen Luo Wei Liu Lei Lv Qiong Wu Jinxia Dai Ming Zhou Heyou Han Zhen F. Fu Hui Gong Fan Bai Ling Zhao |
author_facet | Yachun Zhang Xudong Xing Ben Long Yandi Cao Simeng Hu Xiangning Li Yalan Yu Dayong Tian Baokun Sui Zhaochen Luo Wei Liu Lei Lv Qiong Wu Jinxia Dai Ming Zhou Heyou Han Zhen F. Fu Hui Gong Fan Bai Ling Zhao |
author_sort | Yachun Zhang |
collection | DOAJ |
description | Abstract Background Neurotropic virus infection can cause serious damage to the central nervous system (CNS) in both humans and animals. The complexity of the CNS poses unique challenges to investigate the infection of these viruses in the brain using traditional techniques. Methods In this study, we explore the use of fluorescence micro‐optical sectioning tomography (fMOST) and single‐cell RNA sequencing (scRNA‐seq) to map the spatial and cellular distribution of a representative neurotropic virus, rabies virus (RABV), in the whole brain. Mice were inoculated with a lethal dose of a recombinant RABV encoding enhanced green fluorescent protein (EGFP) under different infection routes, and a three‐dimensional (3D) view of RABV distribution in the whole mouse brain was obtained using fMOST. Meanwhile, we pinpointed the cellular distribution of RABV by utilizing scRNA‐seq. Results Our fMOST data provided the 3D view of a neurotropic virus in the whole mouse brain, which indicated that the spatial distribution of RABV in the brain was influenced by the infection route. Interestingly, we provided evidence that RABV could infect multiple nuclei related to fear independent of different infection routes. More surprisingly, our scRNA‐seq data revealed that besides neurons RABV could infect macrophages and the infiltrating macrophages played at least three different antiviral roles during RABV infection. Conclusion This study draws a comprehensively spatial and cellular map of typical neurotropic virus infection in the mouse brain, providing a novel and insightful strategy to investigate the pathogenesis of RABV and other neurotropic viruses. |
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institution | Directory Open Access Journal |
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language | English |
last_indexed | 2024-04-11T18:17:09Z |
publishDate | 2022-01-01 |
publisher | Wiley |
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series | Clinical and Translational Medicine |
spelling | doaj.art-20fea2887a5e44faa8b80e5ed87f6a882022-12-22T04:09:51ZengWileyClinical and Translational Medicine2001-13262022-01-01121n/an/a10.1002/ctm2.700A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencingYachun Zhang0Xudong Xing1Ben Long2Yandi Cao3Simeng Hu4Xiangning Li5Yalan Yu6Dayong Tian7Baokun Sui8Zhaochen Luo9Wei Liu10Lei Lv11Qiong Wu12Jinxia Dai13Ming Zhou14Heyou Han15Zhen F. Fu16Hui Gong17Fan Bai18Ling Zhao19State Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaBiomedical Pioneering Innovation Center (BIOPIC) School of Life Sciences Peking University Beijing ChinaKey Laboratory of Biomedical Engineering of Hainan Province School of Biomedical Engineering Hainan University Haikou ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaBiomedical Pioneering Innovation Center (BIOPIC) School of Life Sciences Peking University Beijing ChinaBritton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Key Laboratory of Biomedical Photonics of Ministry of Education Huazhong University of Science and Technology Wuhan ChinaBritton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Key Laboratory of Biomedical Photonics of Ministry of Education Huazhong University of Science and Technology Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaBritton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Key Laboratory of Biomedical Photonics of Ministry of Education Huazhong University of Science and Technology Wuhan ChinaBiomedical Pioneering Innovation Center (BIOPIC) School of Life Sciences Peking University Beijing ChinaState Key Laboratory of Agricultural Microbiology Huazhong Agricultural University Wuhan ChinaAbstract Background Neurotropic virus infection can cause serious damage to the central nervous system (CNS) in both humans and animals. The complexity of the CNS poses unique challenges to investigate the infection of these viruses in the brain using traditional techniques. Methods In this study, we explore the use of fluorescence micro‐optical sectioning tomography (fMOST) and single‐cell RNA sequencing (scRNA‐seq) to map the spatial and cellular distribution of a representative neurotropic virus, rabies virus (RABV), in the whole brain. Mice were inoculated with a lethal dose of a recombinant RABV encoding enhanced green fluorescent protein (EGFP) under different infection routes, and a three‐dimensional (3D) view of RABV distribution in the whole mouse brain was obtained using fMOST. Meanwhile, we pinpointed the cellular distribution of RABV by utilizing scRNA‐seq. Results Our fMOST data provided the 3D view of a neurotropic virus in the whole mouse brain, which indicated that the spatial distribution of RABV in the brain was influenced by the infection route. Interestingly, we provided evidence that RABV could infect multiple nuclei related to fear independent of different infection routes. More surprisingly, our scRNA‐seq data revealed that besides neurons RABV could infect macrophages and the infiltrating macrophages played at least three different antiviral roles during RABV infection. Conclusion This study draws a comprehensively spatial and cellular map of typical neurotropic virus infection in the mouse brain, providing a novel and insightful strategy to investigate the pathogenesis of RABV and other neurotropic viruses.https://doi.org/10.1002/ctm2.700fearfMOST technologymacrophagesNK cellsrabies virussingle‐cell RNA‐seq |
spellingShingle | Yachun Zhang Xudong Xing Ben Long Yandi Cao Simeng Hu Xiangning Li Yalan Yu Dayong Tian Baokun Sui Zhaochen Luo Wei Liu Lei Lv Qiong Wu Jinxia Dai Ming Zhou Heyou Han Zhen F. Fu Hui Gong Fan Bai Ling Zhao A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencing Clinical and Translational Medicine fear fMOST technology macrophages NK cells rabies virus single‐cell RNA‐seq |
title | A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencing |
title_full | A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencing |
title_fullStr | A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencing |
title_full_unstemmed | A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencing |
title_short | A spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fMOST and single‐cell RNA sequencing |
title_sort | spatial and cellular distribution of rabies virus infection in the mouse brain revealed by fmost and single cell rna sequencing |
topic | fear fMOST technology macrophages NK cells rabies virus single‐cell RNA‐seq |
url | https://doi.org/10.1002/ctm2.700 |
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