학술논문
Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue.
Document Type
Academic Journal
Author
Shi G; HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.; Li T; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.; Lai KK; HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.; Johnson RF; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.; Yewdell JW; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.; Compton AA; HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA. alex.compton@nih.gov.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
Omicron emerged following COVID-19 vaccination campaigns, displaced previous SARS-CoV-2 variants of concern worldwide, and gave rise to lineages that continue to spread. Here, we show that Omicron exhibits increased infectivity in primary adult upper airway tissue relative to Delta. Using recombinant forms of SARS-CoV-2 and nasal epithelial cells cultured at the liquid-air interface, we show that mutations unique to Omicron Spike enable enhanced entry into nasal tissue. Unlike earlier variants of SARS-CoV-2, our findings suggest that Omicron enters nasal cells independently of serine transmembrane proteases and instead relies upon metalloproteinases to catalyze membrane fusion. Furthermore, we demonstrate that this entry pathway unlocked by Omicron Spike enables evasion from constitutive and interferon-induced antiviral factors that restrict SARS-CoV-2 entry following attachment. Therefore, the increased transmissibility exhibited by Omicron in humans may be attributed not only to its evasion of vaccine-elicited adaptive immunity, but also to its superior invasion of nasal epithelia and resistance to the cell-intrinsic barriers present therein.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)