Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating.
| العنوان: | Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating. |
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| المؤلفون: | Tanneti NS; Department of Microbiology., Patel AK; Department of Microbiology., Tan LH; Department of Otorhinolaryngology- Head and Neck Surgery., Marques AD; Department of Microbiology., Perera RAPM; Department of Microbiology., Sherrill-Mix S; Department of Microbiology., Kelly BJ; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA., Renner DM; Department of Microbiology., Collman RG; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA., Rodino K; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA., Lee C; Department of Microbiology., Bushman FD; Department of Microbiology., Cohen NA; Department of Otorhinolaryngology- Head and Neck Surgery.; Corporal Michael J. Crescenz VA Medical Center, Surgical Services, Philadelphia, USA.; Monell Chemical Senses Center, Philadelphia, USA., Weiss SR; Department of Microbiology. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 21. Date of Electronic Publication: 2023 Dec 21. |
| 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: | The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants of concern (VOCs) due to selection and rapid circulation in the human population. Here we elucidate functional features of each VOC linked to variations in replication rate. Patient-derived primary nasal cultures grown at air-liquid-interface (ALI) were used to model upper-respiratory infection and human lung epithelial cell lines used to model lower-respiratory infection. All VOCs replicated to higher titers than the ancestral virus, suggesting a selection for replication efficiency. In primary nasal cultures, Omicron replicated to the highest titers at early time points, followed by Delta, paralleling comparative studies of population sampling. All SARS-CoV-2 viruses entered the cell primarily via a transmembrane serine protease 2 (TMPRSS2)-dependent pathway, and Omicron was more likely to use an endosomal route of entry. All VOCs activated and overcame dsRNA-induced cellular responses including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation and protein kinase R activation. Among the VOCs, Omicron infection induced expression of the most IFN and IFN stimulated genes. Infections in nasal cultures resulted in cellular damage, including a compromise of cell-barrier integrity and loss of nasal cilia and ciliary beating function, especially during Delta infection. Overall, Omicron was optimized for replication in the upper-respiratory system and least-favorable in the lower-respiratory cell line; and Delta was the most cytopathic for both upper and lower respiratory cells. Our findings highlight the functional differences among VOCs at the cellular level and imply distinct mechanisms of pathogenesis in infected individuals. |
| التعليقات: | Update in: mBio. 2024 Mar 13;:e0312923. (PMID: 38477472) |
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| معلومات مُعتمدة: | R01 AI169537 United States AI NIAID NIH HHS; I01 BX005432 United States BX BLRD VA; P30 AI045008 United States AI NIAID NIH HHS; T32 NS043126 United States NS NINDS NIH HHS; R01 AI140442 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: COVID-19; SARS-CoV-2; dsRNA; primary nasal cultures; spike cleavage; variants of concern |
| تواريخ الأحداث: | Date Created: 20230904 Latest Revision: 20240410 |
| رمز التحديث: | 20240410 |
| مُعرف محوري في PubMed: | PMC10473756 |
| DOI: | 10.1101/2023.08.24.553565 |
| PMID: | 37662273 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.08.24.553565 |
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