The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys

Abstract Neurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 inv...

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Main Authors: Li Jiao, Yun Yang, Wenhai Yu, Yuan Zhao, Haiting Long, Jiahong Gao, Kaiyun Ding, Chunxia Ma, Jingmei Li, Siwen Zhao, Haixuan Wang, Haiyan Li, Mengli Yang, Jingwen Xu, Junbin Wang, Jing Yang, Dexuan Kuang, Fangyu Luo, Xingli Qian, Longjiang Xu, Bin Yin, Wei Liu, Hongqi Liu, Shuaiyao Lu, Xiaozhong Peng
Format: Article
Language:English
Published: Nature Publishing Group 2021-04-01
Series:Signal Transduction and Targeted Therapy
Online Access:https://doi.org/10.1038/s41392-021-00591-7
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author Li Jiao
Yun Yang
Wenhai Yu
Yuan Zhao
Haiting Long
Jiahong Gao
Kaiyun Ding
Chunxia Ma
Jingmei Li
Siwen Zhao
Haixuan Wang
Haiyan Li
Mengli Yang
Jingwen Xu
Junbin Wang
Jing Yang
Dexuan Kuang
Fangyu Luo
Xingli Qian
Longjiang Xu
Bin Yin
Wei Liu
Hongqi Liu
Shuaiyao Lu
Xiaozhong Peng
author_facet Li Jiao
Yun Yang
Wenhai Yu
Yuan Zhao
Haiting Long
Jiahong Gao
Kaiyun Ding
Chunxia Ma
Jingmei Li
Siwen Zhao
Haixuan Wang
Haiyan Li
Mengli Yang
Jingwen Xu
Junbin Wang
Jing Yang
Dexuan Kuang
Fangyu Luo
Xingli Qian
Longjiang Xu
Bin Yin
Wei Liu
Hongqi Liu
Shuaiyao Lu
Xiaozhong Peng
author_sort Li Jiao
collection DOAJ
description Abstract Neurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 invades the CNS primarily via the olfactory bulb. Thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. The infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons, microglia, and astrocytes in the CNS. Consistently, SARS-CoV-2 infects neuro-derived SK-N-SH, glial-derived U251, and brain microvascular endothelial cells in vitro. To our knowledge, this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model, which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.
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spelling doaj.art-3d2f48ca49c5490dab9b3d0716a2dd2d2022-12-21T21:30:47ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352021-04-016111110.1038/s41392-021-00591-7The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeysLi Jiao0Yun Yang1Wenhai Yu2Yuan Zhao3Haiting Long4Jiahong Gao5Kaiyun Ding6Chunxia Ma7Jingmei Li8Siwen Zhao9Haixuan Wang10Haiyan Li11Mengli Yang12Jingwen Xu13Junbin Wang14Jing Yang15Dexuan Kuang16Fangyu Luo17Xingli Qian18Longjiang Xu19Bin Yin20Wei Liu21Hongqi Liu22Shuaiyao Lu23Xiaozhong Peng24National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeState Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeDepartment of Anatomy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeNational Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Neurological manifestations are frequently reported in the COVID-19 patients. Neuromechanism of SARS-CoV-2 remains to be elucidated. In this study, we explored the mechanisms of SARS-CoV-2 neurotropism via our established non-human primate model of COVID-19. In rhesus monkey, SARS-CoV-2 invades the CNS primarily via the olfactory bulb. Thereafter, viruses rapidly spread to functional areas of the central nervous system, such as hippocampus, thalamus, and medulla oblongata. The infection of SARS-CoV-2 induces the inflammation possibly by targeting neurons, microglia, and astrocytes in the CNS. Consistently, SARS-CoV-2 infects neuro-derived SK-N-SH, glial-derived U251, and brain microvascular endothelial cells in vitro. To our knowledge, this is the first experimental evidence of SARS-CoV-2 neuroinvasion in the NHP model, which provides important insights into the CNS-related pathogenesis of SARS-CoV-2.https://doi.org/10.1038/s41392-021-00591-7
spellingShingle Li Jiao
Yun Yang
Wenhai Yu
Yuan Zhao
Haiting Long
Jiahong Gao
Kaiyun Ding
Chunxia Ma
Jingmei Li
Siwen Zhao
Haixuan Wang
Haiyan Li
Mengli Yang
Jingwen Xu
Junbin Wang
Jing Yang
Dexuan Kuang
Fangyu Luo
Xingli Qian
Longjiang Xu
Bin Yin
Wei Liu
Hongqi Liu
Shuaiyao Lu
Xiaozhong Peng
The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys
Signal Transduction and Targeted Therapy
title The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys
title_full The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys
title_fullStr The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys
title_full_unstemmed The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys
title_short The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys
title_sort olfactory route is a potential way for sars cov 2 to invade the central nervous system of rhesus monkeys
url https://doi.org/10.1038/s41392-021-00591-7
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