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Emerg. Microbes Infect., Dec 2022, 11 (1) | https://doi.org/10.1080/22221751.2021.2024095 Direct neuronal infection of SARS-CoV-2 reveals cellular and molecular pathology of chemosensory impairment of COVID-19 patients

Kwang-Soo Lyoo^a*, Hyeon Myeong Kim^b*, Bina Lee^c*, Young Hyun Che^b, Seong-Jae Kim^d, Daesub Song^e, Woochang Hwang^f, Sun Lee^g, Jae-Hoon Park^g, Woonsung Na^h, Seung Pil Yuncan^d Yong Jun Kim^b,g

^aKorea Zoonosis Research Institute, Jeonbuk National University, Iksan, Korea;

^bDepartment of Biomedical Science, Graduate School,Kyung Hee University, Seoul, Korea;

^cDepartment of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Korea;

^dDepartment of Ophthalmology, Institute of Health Sciences, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea;

^eDepartment of Pharmacy, Korea University, Sejong, Korea;

^fBiostatistical Consulting and Research Lab, Medical Research Collaborating Center, Hanyang University, Seoul, Korea;

^gDepartment ofPathology, School of Medicine, Kyung Hee University, Seoul, Korea;

^hDepartment of Veterinary Virology, College of Veterinary Medicine,Chonnam National University, Gwangju, Korea

These authors contributed equally: Kwang-Soo Lyoo, Hyeon Myeong Kim, Bina Lee

Correspondence : Woonsung Na, Seung Pil Yuncan Yong Jun Kim

Abstract

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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게재일2022년 12월 (BRIC 등록일 2024-01-22)
연구진국내 연구진
분야 의약학 > 감염의학

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