期刊
EMERGING MICROBES & INFECTIONS
卷 11, 期 1, 页码 406-411出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/22221751.2021.2024095
关键词
SARS-CoV-2; viral infection; infection modelling; chemosensory impairment; hESC-derived peripheral neurons
资金
- National Research Foundation of Korea [NRF-2019R1I1A3A01061034]
- Institute of Health Sciences of Gyeongsang National University [IHS GNU-2019-01]
This study found that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect human peripheral sensory neurons, leading to molecular pathogenesis for chemosensory impairments. By using a model of peripheral neurons derived from human embryonic stem cells, we revealed the cellular and molecular pathologies responsible for symptoms experienced by COVID-19 patients in the early stages of infection or as sequelae.
Y Patients with recent pandemic coronavirus disease 19 (COVID-19) complain of neurological abnormalities in sensory functions such as smell and taste in the early stages of infection. Determining the cellular and molecular mechanism of sensory impairment is critical to understand the pathogenesis of clinical manifestations, as well as in setting therapeutic targets for sequelae and recurrence. The absence of studies utilizing proper models of human peripheral nerve hampers an understanding of COVID-19 pathogenesis. Here, we report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects human peripheral sensory neurons, leading to molecular pathogenesis for chemosensory impairments. An in vitro system utilizing human embryonic stem cell (hESC)-derived peripheral neurons was used to model the cellular and molecular pathologies responsible for symptoms that most COVID-19 patients experience early in infection or may develop as sequelae. Peripheral neurons differentiated from hESCs expressed viral entry factor ACE2, and were directly infected with SARS-CoV-2 via ACE2. Human peripheral neurons infected with SARS-CoV-2 exhibited impaired molecular features of chemosensory function associated with abnormalities in sensory neurons of the olfactory or gustatory organs. Our results provide new insights into the pathogenesis of chemosensory dysfunction in patients with COVID-19.
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