This article is a Preprint
Preprints are preliminary research reports that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Preprints posted online allow authors to receive rapid feedback and the entire scientific community can appraise the work for themselves and respond appropriately. Those comments are posted alongside the preprints for anyone to read them and serve as a post publication assessment.
Evolution of enhanced innate immune evasion by the SARS-CoV-2 B.1.1.7 UK variant (preprint)
biorxiv; 2021.
Preprint
in English
| bioRxiv | ID: ppzbmed-10.1101.2021.06.06.446826
ABSTRACT
Emergence of SARS-CoV-2 variants, including the globally successful B.1.1.7 lineage, suggests viral adaptations to host selective pressures resulting in more efficient transmission. Although much effort has focused on Spike adaptation for viral entry and adaptive immune escape, B.1.1.7 mutations outside Spike likely contribute to enhance transmission. Here we used unbiased abundance proteomics, phosphoproteomics, mRNA sequencing and viral replication assays to show that B.1.1.7 isolates more effectively suppress host innate immune responses in airway epithelial cells. We found that B.1.1.7 isolates have dramatically increased subgenomic RNA and protein levels of Orf9b and Orf6, both known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein required for RNA sensing adaptor MAVS activation, and Orf9b binding and activity was regulated via phosphorylation. We conclude that B.1.1.7 has evolved beyond the Spike coding region to more effectively antagonise host innate immune responses through upregulation of specific subgenomic RNA synthesis and increased protein expression of key innate immune antagonists. We propose that more effective innate immune antagonism increases the likelihood of successful B.1.1.7 transmission, and may increase in vivo replication and duration of infection.
Full text:
Available
Collection:
Preprints
Database:
bioRxiv
Language:
English
Year:
2021
Document Type:
Preprint
Similar
MEDLINE
...
LILACS
LIS