tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2022 May 24;119(21):e2123208119.
doi: 10.1073/pnas.2123208119. Epub 2022 May 20.
MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells
Courtney E Comar[SUP] 1 2 [/SUP], Clayton J Otter[SUP] 1 2 [/SUP], Jessica Pfannenstiel[SUP] 3 [/SUP], Ethan Doerger[SUP] 3 [/SUP], David M Renner[SUP] 1 2 [/SUP], Li Hui Tan[SUP] 4 [/SUP], Stanley Perlman[SUP] 5 [/SUP], Noam A Cohen[SUP] 4 6 [/SUP], Anthony R Fehr[SUP] 3 5 [/SUP], Susan R Weiss[SUP] 1 2 [/SUP]
Affiliations
Abstract
SignificanceMiddle East respiratory syndrome coronavirus (MERS-CoV) causes highly lethal respiratory disease. MERS-CoV encodes innate immune antagonists, including accessory proteins NS4a and NS4b, unique to the merbeco lineage of betacoronaviruses, 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 is thus more vulnerable to host innate immune responses.
Keywords: MERS-CoV; PKR; RNase L; endonuclease U; innate immune antagonism.
. 2022 May 24;119(21):e2123208119.
doi: 10.1073/pnas.2123208119. Epub 2022 May 20.
MERS-CoV endoribonuclease and accessory proteins jointly evade host innate immunity during infection of lung and nasal epithelial cells
Courtney E Comar[SUP] 1 2 [/SUP], Clayton J Otter[SUP] 1 2 [/SUP], Jessica Pfannenstiel[SUP] 3 [/SUP], Ethan Doerger[SUP] 3 [/SUP], David M Renner[SUP] 1 2 [/SUP], Li Hui Tan[SUP] 4 [/SUP], Stanley Perlman[SUP] 5 [/SUP], Noam A Cohen[SUP] 4 6 [/SUP], Anthony R Fehr[SUP] 3 5 [/SUP], Susan R Weiss[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35594398
- DOI: 10.1073/pnas.2123208119
Abstract
SignificanceMiddle East respiratory syndrome coronavirus (MERS-CoV) causes highly lethal respiratory disease. MERS-CoV encodes innate immune antagonists, including accessory proteins NS4a and NS4b, unique to the merbeco lineage of betacoronaviruses, 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 is thus more vulnerable to host innate immune responses.
Keywords: MERS-CoV; PKR; RNase L; endonuclease U; innate immune antagonism.