tetano
Editor, Senior Moderator
Cell Rep
. 2022 Mar 8;38(10):110434.
doi: 10.1016/j.celrep.2022.110434.
The RNA helicase DHX16 recognizes specific viral RNA to trigger RIG-I-dependent innate antiviral immunity
Adam Hage[SUP] 1 [/SUP], Preeti Bharaj[SUP] 1 [/SUP], Sarah van Tol[SUP] 1 [/SUP], Maria I Giraldo[SUP] 1 [/SUP], Maria Gonzalez-Orozco[SUP] 1 [/SUP], Karl M Valerdi[SUP] 1 [/SUP], Abbey N Warren[SUP] 2 [/SUP], Leopoldo Aguilera-Aguirre[SUP] 1 [/SUP], Xuping Xie[SUP] 3 [/SUP], Steven G Widen[SUP] 3 [/SUP], Hong M Moulton[SUP] 4 [/SUP], Benhur Lee[SUP] 5 [/SUP], Jeffrey R Johnson[SUP] 5 [/SUP], Nevan J Krogan[SUP] 6 [/SUP], Adolfo García-Sastre[SUP] 7 [/SUP], Pei-Yong Shi[SUP] 8 [/SUP], Alexander N Freiberg[SUP] 9 [/SUP], Ricardo Rajsbaum[SUP] 10 [/SUP]
Affiliations
Abstract
Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses. However, few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue. We identified the RNA helicase DHX16 as a potential pattern recognition receptor (PRR). Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. These effects extended to members of other virus families, including Zika and SARS-CoV-2. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6. DHX16 recognizes a signal in influenza RNA segments that undergo splicing and requires its RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a PRR that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored poly-Ub.
Keywords: DHX16; RIG-I; SARS-CoV-2; TRIM6; influenza A virus; innate immunity; splicing; tripartite motif (TRIM) protein; type I interferon; unanchored ubiquitin.
. 2022 Mar 8;38(10):110434.
doi: 10.1016/j.celrep.2022.110434.
The RNA helicase DHX16 recognizes specific viral RNA to trigger RIG-I-dependent innate antiviral immunity
Adam Hage[SUP] 1 [/SUP], Preeti Bharaj[SUP] 1 [/SUP], Sarah van Tol[SUP] 1 [/SUP], Maria I Giraldo[SUP] 1 [/SUP], Maria Gonzalez-Orozco[SUP] 1 [/SUP], Karl M Valerdi[SUP] 1 [/SUP], Abbey N Warren[SUP] 2 [/SUP], Leopoldo Aguilera-Aguirre[SUP] 1 [/SUP], Xuping Xie[SUP] 3 [/SUP], Steven G Widen[SUP] 3 [/SUP], Hong M Moulton[SUP] 4 [/SUP], Benhur Lee[SUP] 5 [/SUP], Jeffrey R Johnson[SUP] 5 [/SUP], Nevan J Krogan[SUP] 6 [/SUP], Adolfo García-Sastre[SUP] 7 [/SUP], Pei-Yong Shi[SUP] 8 [/SUP], Alexander N Freiberg[SUP] 9 [/SUP], Ricardo Rajsbaum[SUP] 10 [/SUP]
Affiliations
- PMID: 35263596
- DOI: 10.1016/j.celrep.2022.110434
Abstract
Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses. However, few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue. We identified the RNA helicase DHX16 as a potential pattern recognition receptor (PRR). Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. These effects extended to members of other virus families, including Zika and SARS-CoV-2. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6. DHX16 recognizes a signal in influenza RNA segments that undergo splicing and requires its RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a PRR that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored poly-Ub.
Keywords: DHX16; RIG-I; SARS-CoV-2; TRIM6; influenza A virus; innate immunity; splicing; tripartite motif (TRIM) protein; type I interferon; unanchored ubiquitin.