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10.1038/s41590-021-01035-8 http://scihub22266oqcxt.onion/10.1038/s41590-021-01035-8 34663977!ä!34663977 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\34663977.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Nat+Immunol 2021 ; 22 (11): 1416-1427 Nephropedia Template TP {{tp|p=34663977|t=2021. Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection |pdf=|usr=}}{{34663977}} gab.com Text Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection JO: Nat Immunol http://www.kidney.de/pget.php?&tw=1&pmid=34663977 #FOAvip Ubiquitin-like protein ISG15 (interferon-stimulated gene 15) (ISG15) is a ubiquitin-like modifier induced during infections and involved in host defense mechanisms. Not surprisingly, many viruses encode deISGylating activities to antagonize its effect. Here we show that infection by Zika, SARS-CoV-2 and influenza viruses induce ISG15-modifying enzymes. While influenza and Zika viruses induce ISGylation, SARS-CoV-2 triggers deISGylation instead to generate free ISG15. The ratio of free versus conjugated ISG15 driven by the papain-like protease (PLpro) enzyme of SARS-CoV-2 correlates with macrophage polarization toward a pro-inflammatory phenotype and attenuated antigen presentation. In vitro characterization of purified wild-type and mutant PLpro revealed its strong deISGylating over deubiquitylating activity. Quantitative proteomic analyses of PLpro substrates and secretome from SARS-CoV-2-infected macrophages revealed several glycolytic enzymes previously implicated in the expression of inflammatory genes and pro-inflammatory cytokines, respectively. Collectively, our results indicate that altered free versus conjugated ISG15 dysregulates macrophage responses and probably contributes to the cytokine storms triggered by SARS-CoV-2. Twit Text FOAVip Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection ????Nat Immunol http://www.kidney.de/pget.php?&tw=1&pmid=34663977 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34663977 #FOAvip English Wikipedia <ref>{{Cite pmid|34663977}}</ref> Altered ISGylation drives aberrant macrophage-dependent immune responses during SARS-CoV-2 infection #MMPMID34663977 Munnur D; Teo Q; Eggermont D; Lee HHY; Thery F; Ho J; van Leur SW; Ng WWS; Siu LYL; Beling A; Ploegh H; Pinto-Fernandez A; Damianou A; Kessler B; Impens F; Mok CKP; Sanyal S Nat Immunol 2021[Nov]; 22 (11): 1416-1427 PMID34663977show ga Ubiquitin-like protein ISG15 (interferon-stimulated gene 15) (ISG15) is a ubiquitin-like modifier induced during infections and involved in host defense mechanisms. Not surprisingly, many viruses encode deISGylating activities to antagonize its effect. Here we show that infection by Zika, SARS-CoV-2 and influenza viruses induce ISG15-modifying enzymes. While influenza and Zika viruses induce ISGylation, SARS-CoV-2 triggers deISGylation instead to generate free ISG15. The ratio of free versus conjugated ISG15 driven by the papain-like protease (PLpro) enzyme of SARS-CoV-2 correlates with macrophage polarization toward a pro-inflammatory phenotype and attenuated antigen presentation. In vitro characterization of purified wild-type and mutant PLpro revealed its strong deISGylating over deubiquitylating activity. Quantitative proteomic analyses of PLpro substrates and secretome from SARS-CoV-2-infected macrophages revealed several glycolytic enzymes previously implicated in the expression of inflammatory genes and pro-inflammatory cytokines, respectively. Collectively, our results indicate that altered free versus conjugated ISG15 dysregulates macrophage responses and probably contributes to the cytokine storms triggered by SARS-CoV-2. |COVID-19/*immunology[MESH] |Cell Differentiation[MESH] |Coronavirus Papain-Like Proteases/metabolism[MESH] |Cytokines/genetics/*metabolism[MESH] |Gene Knockdown Techniques[MESH] |HeLa Cells[MESH] |Humans[MESH] |Immune Evasion[MESH] |Immunity, Innate[MESH] |Inflammation/*immunology[MESH] |Influenza A virus/physiology[MESH] |Influenza, Human/immunology[MESH] |Macrophages/*immunology[MESH] |Pluripotent Stem Cells/cytology[MESH] |SARS-CoV-2/*physiology[MESH] |Ubiquitination[MESH] |Ubiquitins/genetics/*metabolism[MESH] |Zika Virus Infection/immunology[MESH]Altered ISGylation drives aberrant macrophage-dependent immune respons(epmc).pdf DeepDyve Pubget Overpricing