tetano
Editor, Senior Moderator
Cell Rep. 2020 Feb 4;30(5):1570-1584.e6. doi: 10.1016/j.celrep.2020.01.015. [h=1]OTUB1 Is a Key Regulator of RIG-I-Dependent Immune Signaling and Is Targeted for Proteasomal Degradation by Influenza A NS1.[/h]
Jahan AS[SUP]1[/SUP], Biquand E[SUP]2[/SUP], Mu?oz-Moreno R[SUP]3[/SUP], Le Quang A[SUP]1[/SUP], Mok CK[SUP]1[/SUP], Wong HH[SUP]1[/SUP], Teo QW[SUP]1[/SUP], Valkenburg SA[SUP]1[/SUP], Chin AWH[SUP]4[/SUP], Man Poon LL[SUP]4[/SUP], Te Velthuis A[SUP]5[/SUP], Garc?a-Sastre A[SUP]6[/SUP], Demeret C[SUP]2[/SUP], Sanyal S[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Deubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [[SUP]35[/SUP]S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses.
Copyright ? 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] RIG-I signaling; RNA virus; deubiquitylases; influenza A; innate immune response; ubiquitylation; viral subversion strategies
PMID: 32023470 DOI: 10.1016/j.celrep.2020.01.015
Jahan AS[SUP]1[/SUP], Biquand E[SUP]2[/SUP], Mu?oz-Moreno R[SUP]3[/SUP], Le Quang A[SUP]1[/SUP], Mok CK[SUP]1[/SUP], Wong HH[SUP]1[/SUP], Teo QW[SUP]1[/SUP], Valkenburg SA[SUP]1[/SUP], Chin AWH[SUP]4[/SUP], Man Poon LL[SUP]4[/SUP], Te Velthuis A[SUP]5[/SUP], Garc?a-Sastre A[SUP]6[/SUP], Demeret C[SUP]2[/SUP], Sanyal S[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Deubiquitylases (DUBs) regulate critical signaling pathways at the intersection of host immunity and viral pathogenesis. Although RIG-I activation is heavily dependent on ubiquitylation, systematic analyses of DUBs that regulate this pathway have not been performed. Using a ubiquitin C-terminal electrophile, we profile DUBs that function during influenza A virus (IAV) infection and isolate OTUB1 as a key regulator of RIG-I-dependent antiviral responses. Upon infection, OTUB1 relocalizes from the nucleus to mitochondrial membranes together with RIG-I, viral PB2, and NS1. Its expression depends on competing effects of interferon stimulation and IAV-triggered degradation. OTUB1 activates RIG-I via a dual mechanism of K48 polyubiquitin hydrolysis and formation of an E2-repressive complex with UBCH5c. We reconstitute this mechanism in a cell-free system comprising [[SUP]35[/SUP]S]IRF3, purified RIG-I, mitochondrial membranes, and cytosol expressing OTUB1 variants. A range of IAV NS1 proteins trigger proteasomal degradation of OTUB1, antagonizing the RIG-I signaling cascade and antiviral responses.
Copyright ? 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] RIG-I signaling; RNA virus; deubiquitylases; influenza A; innate immune response; ubiquitylation; viral subversion strategies
PMID: 32023470 DOI: 10.1016/j.celrep.2020.01.015