Li Jiao1, Yun Yang1, Wenhai Yu1, Yuan Zhao1, Haiting Long1, Jiahong Gao1, Kaiyun Ding1, Chunxia Ma1, Jingmei Li1, Siwen Zhao1, Haixuan Wang1, Haiyan Li1, Mengli Yang1, Jingwen Xu1, Junbin Wang1, Jing Yang1, Dexuan Kuang1, Fangyu Luo1, Xingli Qian1, Longjiang Xu1, Bin Yin2, Wei Liu3, Hongqi Liu4, Shuaiyao Lu5,6, Xiaozhong Peng7,8. 1. National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China. 2. State 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 College, Beijing, China. 3. Department of Anatomy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China. 4. National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China. lhq@imbcams.com.cn. 5. National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China. lushuaiyao-km@163.com. 6. State 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 College, Beijing, China. lushuaiyao-km@163.com. 7. National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan, China. pengxiaozhong@pumc.edu.cn. 8. State 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 College, Beijing, China. pengxiaozhong@pumc.edu.cn.
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.
Neurological manifestations are frequently reported in the n class="Disease">COVID-19patients. 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.
Authors: Geidy E Serrano; Jessica E Walker; Cécilia Tremblay; Ignazio S Piras; Matthew J Huentelman; Christine M Belden; Danielle Goldfarb; David Shprecher; Alireza Atri; Charles H Adler; Holly A Shill; Erika Driver-Dunckley; Shyamal H Mehta; Richard Caselli; Bryan K Woodruff; Chadwick F Haarer; Thomas Ruhlen; Maria Torres; Steve Nguyen; Dasan Schmitt; Steven Z Rapscak; Christian Bime; Joseph L Peters; Ellie Alevritis; Richard A Arce; Michael J Glass; Daisy Vargas; Lucia I Sue; Anthony J Intorcia; Courtney M Nelson; Javon Oliver; Aryck Russell; Katsuko E Suszczewicz; Claryssa I Borja; Madison P Cline; Spencer J Hemmingsen; Sanaria Qiji; Holly M Hobgood; Joseph P Mizgerd; Malaya K Sahoo; Haiyu Zhang; Daniel Solis; Thomas J Montine; Gerald J Berry; Eric M Reiman; Katharina Röltgen; Scott D Boyd; Benjamin A Pinsky; James L Zehnder; Pierre Talbot; Marc Desforges; Michael DeTure; Dennis W Dickson; Thomas G Beach Journal: J Neuropathol Exp Neurol Date: 2022-08-16 Impact factor: 3.148
Authors: Shambhunath Choudhary; Isis Kanevsky; Soner Yildiz; Rani S Sellers; Kena A Swanson; Tania Franks; Raveen Rathnasinghe; Raquel Munoz-Moreno; Sonia Jangra; Olga Gonzalez; Philip Meade; Timothy Coskran; Jessie Qian; Thomas A Lanz; Jillian G Johnson; Cassandra A Tierney; Justin D Smith; Kristin Tompkins; Arthur Illenberger; Paula Corts; Tara Ciolino; Philip R Dormitzer; Edward J Dick; Vinay Shivanna; Shannan Hall-Ursone; Journey Cole; Deepak Kaushal; Jane A Fontenot; Carles Martinez-Romero; Meagan McMahon; Florian Krammer; Michael Schotsaert; Adolfo García-Sastre Journal: Toxicol Pathol Date: 2022-02-05 Impact factor: 1.930
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