| http://purl.uniprot.org/citations/29263274 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29263274 | http://www.w3.org/2000/01/rdf-schema#comment | "Retinoic acid-inducible gene I (RIG-I) is a key pattern recognition receptor that senses viral RNA and interacts with the mitochondrial adaptor MAVS, triggering a signaling cascade that results in the production of type I interferons (IFNs). This signaling axis is initiated by K63-linked ubiquitination of RIG-I mediated by the E3 ubiquitin ligase TRIM25, which promotes the interaction of RIG-I with MAVS. USP15 was recently identified as an upstream regulator of TRIM25, stabilizing the enzyme through removal of degradative K48-linked polyubiquitin, ultimately promoting RIG-I-dependent cytokine responses. Here, we show that the E6 oncoprotein of human papillomavirus type 16 (HPV16) as well as of other HPV types form a complex with TRIM25 and USP15 in human cells. In the presence of E6, the K48-linked ubiquitination of TRIM25 was markedly increased, and in line with this, TRIM25 degradation was enhanced. Our results further showed that E6 inhibited the TRIM25-mediated K63-linked ubiquitination of RIG-I and its CARD-dependent interaction with MAVS. HPV16 E6, but not E7, suppressed the RIG-I-mediated induction of IFN-β, chemokines, and IFN-stimulated genes (ISGs). Finally, CRISPR-Cas9 gene targeting in human keratinocytes showed that the TRIM25-RIG-I-MAVS triad is important for eliciting an antiviral immune response to HPV16 infection. Our study thus identifies a novel immune escape mechanism that is conserved among different HPV strains and further indicates that the RIG-I signaling pathway plays an important role in the innate immune response to HPV infection.IMPORTANCE Persistent infection and tumorigenesis by HPVs are known to require viral manipulation of a variety of cellular processes, including those involved in innate immune responses. Here, we show that the HPV E6 oncoprotein antagonizes the activation of the cytoplasmic innate immune sensor RIG-I by targeting its upstream regulatory enzymes TRIM25 and USP15. We further show that the RIG-I signaling cascade is important for an antiviral innate immune response to HPV16 infection, providing evidence that RIG-I, whose role in sensing RNA virus infections has been well characterized, also plays a crucial role in the antiviral host response to small DNA viruses of the Papillomaviridae family."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.org/dc/terms/identifier | "doi:10.1128/jvi.01737-17"xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Meyers C."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Howley P.M."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Munger K."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Gack M.U."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Meng M."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Chiang C."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Biryukov J."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "White E.A."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Pauli E.K."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/author | "Feister K.F."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/name | "J Virol"xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/pages | "e01737-17"xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/title | "The Human Papillomavirus E6 Oncoprotein Targets USP15 and TRIM25 To Suppress RIG-I-Mediated Innate Immune Signaling."xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://purl.uniprot.org/core/volume | "92"xsd:string |
| http://purl.uniprot.org/citations/29263274 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29263274 |
| http://purl.uniprot.org/citations/29263274 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29263274 |
| http://purl.uniprot.org/uniprot/#_Q14258-mappedCitation-29263274 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29263274 |
| http://purl.uniprot.org/uniprot/#_B3KN51-mappedCitation-29263274 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29263274 |
| http://purl.uniprot.org/uniprot/#_B7Z3J0-mappedCitation-29263274 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29263274 |
| http://purl.uniprot.org/uniprot/#_B4DWT9-mappedCitation-29263274 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29263274 |
| http://purl.uniprot.org/uniprot/#_B4DN46-mappedCitation-29263274 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29263274 |