{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:04:27Z","timestamp":1788458667826,"version":"build-2803163510"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2012,1,15]],"date-time":"2012-01-15T00:00:00Z","timestamp":1326585600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2012,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Dendritic cells (DC) are antigen-presenting cells essential for initiating primary immune responses and therefore an ideal target for viral immune evasion. Varicella-zoster virus (VZV) can productively infect immature human DCs and impair their function as immune effectors by inhibiting their maturation, as evidenced by the expression modulation of functionally important cell surface immune molecules CD80, CD86, CD83, and major histocompatibility complex I. The NF-\u03baB pathway largely regulates the expression of these immune molecules, and therefore we sought to determine whether VZV infection of DCs modulates the NF-\u03baB pathway. Nuclear localization of NF-\u03baB p50 and p65 indicates pathway activation; however, immunofluorescence studies revealed cytoplasmic retention of these NF-\u03baB subunits in VZV-infected DCs. Western blotting revealed phosphorylation of the inhibitor of \u03baB\u03b1 (I\u03baB\u03b1) in VZV-infected DCs, indicating that the pathway is active at this point. We conclude that VZV infection of DC inhibits the NF-\u03baB pathway following protein phosphorylation but before the translocation of NF-\u03baB subunits into the nucleus. An NF-\u03baB reporter assay identified VZV open reading frame 61 (ORF61) as an inhibitor of tumor necrosis factor alpha-induced NF-\u03baB reporter activity. Mutational analysis of ORF61 identified the E3 ubiquitin ligase domain as a region required for NF-\u03baB pathway inhibition. In summary, we provide evidence that VZV inhibits the NF-\u03baB signaling pathway in human DCs and that the E3 ubiquitin ligase domain of ORF61 is required to modulate this pathway. Thus, this work identifies a mechanism by which VZV modulates host immune function.<\/jats:p>","DOI":"10.1128\/jvi.06400-11","type":"journal-article","created":{"date-parts":[[2011,11,17]],"date-time":"2011-11-17T12:27:45Z","timestamp":1321532865000},"page":"1193-1202","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Varicella-Zoster Virus Inhibition of the NF-\u03baB Pathway during Infection of Human Dendritic Cells: Role for Open Reading Frame 61 as a Modulator of NF-\u03baB Activity"],"prefix":"10.1128","volume":"86","author":[{"given":"Elizabeth","family":"Sloan","sequence":"first","affiliation":[{"name":"Centre for Virus Research, Westmead Millennium Institute"},{"name":"Department of Infectious Diseases and Immunology, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Henriquez","sequence":"additional","affiliation":[{"name":"Centre for Virus Research, Westmead Millennium Institute"},{"name":"Department of Infectious Diseases and Immunology, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Kinchington","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology and Molecular Microbiology and Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Slobedman","sequence":"additional","affiliation":[{"name":"Centre for Virus Research, Westmead Millennium Institute"},{"name":"Department of Infectious Diseases and Immunology, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison","family":"Abendroth","sequence":"additional","affiliation":[{"name":"Centre for Virus Research, Westmead Millennium Institute"},{"name":"Department of Infectious Diseases and Immunology, University of Sydney, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"155","article-title":"Varicella-zoster virus immune evasion strategies","volume":"342","author":"Abendroth A","year":"2010","unstructured":"AbendrothA KinchingtonPR SlobedmanB. 2010. 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