Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys...Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys Macaca mulatta(M.mulatta)and Macaca fascicularis(M.fascicularis)and New World monkey Callithrix jacchus(C.jacchus).Infected M.mulatta and M.fascicularis showed abnormal chest radiographs,an increased body temperature and a decreased body weight.Viral genomes were detected in swab and blood samples from all animals.Viral load was detected in the pulmonary tissues of M.mulatta and M.fascicularis but not C.jacchus.Furthermore,among the three animal species,M.mulatta showed the strongest response to SARS-CoV-2,including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues.Collectively,these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M.mulatta as the most suitable for modeling COVID-19.展开更多
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 establishe...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.展开更多
基金supported by the National Research and Development Project of China(2020YFC0841100,2020YFC0846400,and 2020YFA0707600)CAMS Innovation Fund for Medical Sciences(2016-I2M-2-006 and 2020-I2M-CoV19-012)+1 种基金the Talents Project of Yunnan Province(2017HB068)the Special Funds for High-level Health and Family Planning Technical Personnel training of Yunnan Province(D-201653).
文摘Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys Macaca mulatta(M.mulatta)and Macaca fascicularis(M.fascicularis)and New World monkey Callithrix jacchus(C.jacchus).Infected M.mulatta and M.fascicularis showed abnormal chest radiographs,an increased body temperature and a decreased body weight.Viral genomes were detected in swab and blood samples from all animals.Viral load was detected in the pulmonary tissues of M.mulatta and M.fascicularis but not C.jacchus.Furthermore,among the three animal species,M.mulatta showed the strongest response to SARS-CoV-2,including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues.Collectively,these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M.mulatta as the most suitable for modeling COVID-19.
基金This study was supported by the National Key R&D Project of China(2020YFA0707602,2020YFC0846400,2020YFC0841100)CAMS Innovation Fund for Medical Sciences(2016-I2M-2-001,2016-I2M-2-006,and 2020-I2M-COV19-012)+1 种基金Yunnan Key R&D Project(202003AC100003)The Talents Project of Yunnan Province(2017HB068).
文摘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.
