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10.1073/pnas.1921485117 http://scihub22266oqcxt.onion/10.1073/pnas.1921485117 32198201!7149396!32198201     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Proc+Natl+Acad+Sci+U+S+A 2020 ; 117 (14): 8094-8103 Nephropedia Template TP {{tp|p=32198201|t=2020. Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors |pdf=|usr=}}{{32198201}} gab.com Text Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=32198201 #FOAvip Coronaviruses (CoVs) are positive-sense RNA viruses that can emerge from endemic reservoirs and infect zoonotically, causing significant morbidity and mortality. CoVs encode an endoribonuclease designated EndoU that facilitates evasion of host pattern recognition receptor MDA5, but the target of EndoU activity was not known. Here, we report that EndoU cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA, which is the product of polyA-templated RNA synthesis. Using a virus containing an EndoU catalytic-inactive mutation, we detected a higher abundance of PUN RNA in the cytoplasm compared to wild-type-infected cells. Furthermore, we found that transfecting PUN RNA into cells stimulates a robust, MDA5-dependent interferon response, and that removal of the polyuridine extension on the RNA dampens the response. Overall, the results of this study reveal the PUN RNA to be a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP). We also establish a mechanism for EndoU activity to cleave and limit the accumulation of this PAMP. Since EndoU activity is highly conserved in all CoVs, inhibiting this activity may serve as an approach for therapeutic interventions against existing and emerging CoV infections. Twit Text FOAVip Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=32198201 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32198201 #FOAvip English Wikipedia <ref>{{Cite pmid|32198201}}</ref> Coronavirus endoribonuclease targets viral polyuridine sequences to evade activating host sensors #MMPMID32198201 Hackbart M; Deng X; Baker SC Proc Natl Acad Sci U S A 2020[Apr]; 117 (14): 8094-8103 PMID32198201show ga Coronaviruses (CoVs) are positive-sense RNA viruses that can emerge from endemic reservoirs and infect zoonotically, causing significant morbidity and mortality. CoVs encode an endoribonuclease designated EndoU that facilitates evasion of host pattern recognition receptor MDA5, but the target of EndoU activity was not known. Here, we report that EndoU cleaves the 5'-polyuridines from negative-sense viral RNA, termed PUN RNA, which is the product of polyA-templated RNA synthesis. Using a virus containing an EndoU catalytic-inactive mutation, we detected a higher abundance of PUN RNA in the cytoplasm compared to wild-type-infected cells. Furthermore, we found that transfecting PUN RNA into cells stimulates a robust, MDA5-dependent interferon response, and that removal of the polyuridine extension on the RNA dampens the response. Overall, the results of this study reveal the PUN RNA to be a CoV MDA5-dependent pathogen-associated molecular pattern (PAMP). We also establish a mechanism for EndoU activity to cleave and limit the accumulation of this PAMP. Since EndoU activity is highly conserved in all CoVs, inhibiting this activity may serve as an approach for therapeutic interventions against existing and emerging CoV infections. |Animals[MESH] |Antiviral Agents/pharmacology[MESH] |Cell Line[MESH] |Chlorocebus aethiops[MESH] |Coronavirus Infections/*immunology/*virology[MESH] |Coronavirus/enzymology/immunology/*metabolism[MESH] |Endoribonucleases/genetics/*metabolism[MESH] |Host Microbial Interactions/physiology[MESH] |Humans[MESH] |Interferons/pharmacology[MESH] |Poly U/chemistry/*metabolism[MESH] |RNA, Viral/genetics/metabolism[MESH] |Uridine/chemistry[MESH] |Vero Cells[MESH] |Viral Nonstructural Proteins/genetics/*metabolism[MESH]Coronavirus endoribonuclease targets viral polyuridine sequences to ev(epmc).pdf DeepDyve Pubget Overpricing