MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Evolution of enhanced innate immune evasion by SARS-CoV-2

Author(s)
Kellis, Manolis
Thumbnail
DownloadPublished version (31.72Mb)
Publisher with Creative Commons License

Publisher with Creative Commons License

Creative Commons Attribution

Terms of use
Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
Metadata
Show full item record
Abstract
<jats:title>Abstract</jats:title><jats:p>The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission<jats:sup>1,2</jats:sup>. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant<jats:sup>3</jats:sup> suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6—all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection<jats:sup>4</jats:sup>. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.</jats:p>
Date issued
2022
URI
https://hdl.handle.net/1721.1/143721
Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Kellis, Manolis. 2022. "Evolution of enhanced innate immune evasion by SARS-CoV-2." Nature, 602 (7897).
Version: Final published version

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.