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http://purl.uniprot.org/citations/25275128http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25275128http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25275128http://www.w3.org/2000/01/rdf-schema#comment"

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Viral infection frequently triggers activation of host innate immune pathways that attempt to limit viral spread. The NF-κB pathway is a critical component that governs this response. We have found that the human cytomegalovirus (HCMV) U(L)26 protein antagonizes NF-κB activation. Upon infection, an HCMV strain lacking the U(L)26 gene (ΔU(L)26) induced the nuclear translocation of the NF-κB RelB subunit and activated expression and secretion of interleukin-6 (IL-6), an NF-κB target gene. The ΔU(L)26 mutant was also more sensitive to challenge with tumor necrosis factor alpha (TNF-α), a canonical NF-κB inducer. Further, expression of U(L)26 in the absence of other viral proteins blocked NF-κB activation induced by either TNF-α treatment or infection with Sendai virus (SeV). Our results indicate that U(L)26 expression is sufficient to block TNF-α-induced NF-κB nuclear translocation and IκB degradation. Last, U(L)26 blocks TNF-α-induced IκB-kinase (IKK) phosphorylation, a key step in NF-κB activation. Combined, our results indicate that U(L)26 is part of a viral program to antagonize innate immunity through modulation of NF-κB signaling.

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The NF-κB signaling pathway regulates innate immunity, an integral host process that limits viral pathogenesis. Viruses have evolved mechanisms to modulate NF-κB signaling to ensure their replication. HCMV is a major cause of birth defects and disease in immunosuppressed populations. HCMV is known to actively target the NF-κB pathway, which is important for HCMV infection. Our results indicate that the HCMV U(L)26 gene is a key modulator of NF-κB pathway activity. We find the U(L)26 gene is both necessary and sufficient to block NF-κB activation upon challenge with antiviral cytokines. Further, U(L)26 attenuates the phosphorylation and activation of a key NF-κB activating kinase complex, IKK. Our study provides new insight into how HCMV targets the NF-κB pathway. Given its importance to viral infection, the mechanisms through which viruses target the NF-κB pathway highlight areas of vulnerability that could be therapeutically targeted to attenuate viral replication."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.org/dc/terms/identifier"doi:10.1128/jvi.02552-14"xsd:string
http://purl.uniprot.org/citations/25275128http://purl.org/dc/terms/identifier"doi:10.1128/jvi.02552-14"xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Martinez-Sobrido L."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Martinez-Sobrido L."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Mathers C."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Mathers C."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Munger J."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Munger J."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Schafer X."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/author"Schafer X."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/name"J. Virol."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/name"J. Virol."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/pages"14289-14300"xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/pages"14289-14300"xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/title"The human cytomegalovirus UL26 protein antagonizes NF-kappaB activation."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/title"The human cytomegalovirus UL26 protein antagonizes NF-kappaB activation."xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/volume"88"xsd:string
http://purl.uniprot.org/citations/25275128http://purl.uniprot.org/core/volume"88"xsd:string
http://purl.uniprot.org/citations/25275128http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25275128
http://purl.uniprot.org/citations/25275128http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25275128
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