Mutation nsp6 L232F associated with MERS-CoV zoonotic transmission confers higher viral replication in human respiratory tract cultures ex-vivo.
| العنوان: | Mutation nsp6 L232F associated with MERS-CoV zoonotic transmission confers higher viral replication in human respiratory tract cultures ex-vivo. |
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| المؤلفون: | So RT; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China., Chu DK; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; UK Health Security Agency, London, United Kingdom., Hui KP; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China., Mok CK; The Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, PR China.; Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, PR China., Sanyal S; Sir William Dunn School of Pathology, University of Oxford, UK., Nicholls JM; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China., Ho JCW; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China., Cheung MC; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China., Ng KC; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China., Yeung HW; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China., Chan MC; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China., Poon LL; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China., Zhao J; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China., Peiris M; School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.; HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Mar 28. Date of Electronic Publication: 2023 Mar 28. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Middle East respiratory syndrome coronavirus (MERS-CoV) causes zoonotic disease. Dromedary camels are the source of zoonotic infection. We identified a mutation of amino acid leucine to phenylalanine in the codon 232 position of the non-structural protein 6 (nsp6) (nsp6 L232F) that is repeatedly associated with zoonotic transmission. We generated a pair of isogenic recombinant MERS-CoV with nsp6 232L and 232F residues, respectively, and showed that the nsp6 L232F mutation confers higher replication competence in ex-vivo culture of human nasal and bronchial tissues and in lungs of mice experimentally infected in-vivo. Mechanistically, the nsp6 L232F mutation appeared to modulate autophagy and was associated with higher exocytic virus egress, while innate immune responses and zippering activity of the endoplasmic reticulum remained unaffected. Our study suggests that MERS-CoV nsp6 may contribute to viral adaptation to humans. This highlights the importance of continued surveillance of MERS-CoV in both camels and humans. |
| التعليقات: | Update in: J Virol. 2023 Dec 21;97(12):e0136923. (PMID: 38038429) |
| تواريخ الأحداث: | Date Created: 20230410 Latest Revision: 20240101 |
| رمز التحديث: | 20240101 |
| مُعرف محوري في PubMed: | PMC10081289 |
| DOI: | 10.1101/2023.03.27.534490 |
| PMID: | 37034576 |
| قاعدة البيانات: | MEDLINE |
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