MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells.
Courtney E ComarClayton J OtterJessica PfannenstielEthan DoergerDavid M RennerLi Hui TanStanley PerlmanNoam A CohenAnthony R FehrSusan R WeissPublished in: bioRxiv : the preprint server for biology (2021)
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes highly lethal respiratory disease. MERS-CoV encodes several innate immune antagonists, accessory proteins NS4a and NS4b unique to the merbeco lineage and the nsp15 protein endoribonuclease (EndoU), conserved among all coronaviruses. While mutation of each antagonist protein alone has little effect on innate immunity, infections with recombinant MERS-CoVs with mutations of EndoU in combination with either NS4a or NS4b, activate innate signaling pathways and are attenuated for replication. Our data indicate that EndoU and accessory proteins NS4a and NS4b together suppress innate immunity during MERS-CoV infection, to optimize viral replication. This is in contrast to SARS-CoV-2 which activates these pathways and consistent with greater mortality observed during MERS-CoV infection compared to SARS-CoV-2.
Keyphrases
- respiratory syndrome coronavirus
- sars cov
- dengue virus
- coronavirus disease
- zika virus
- innate immune
- immune response
- signaling pathway
- magnetic resonance
- magnetic resonance imaging
- transcription factor
- cardiovascular events
- protein protein
- type diabetes
- small molecule
- single cell
- amino acid
- oxidative stress
- cardiovascular disease
- coronary artery disease
- cell proliferation
- contrast enhanced
- binding protein
- pi k akt
- data analysis