{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:53:40Z","timestamp":1790679220047,"version":"4.1.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2011,10,15]],"date-time":"2011-10-15T00:00:00Z","timestamp":1318636800000},"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":[[2011,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Poxviruses are large DNA viruses that replicate in the cytoplasm of infected cells. Myxoma virus is a rabbit poxvirus that belongs to the\n            <jats:named-content content-type=\"genus-species\">Leporipoxvirus<\/jats:named-content>\n            genus. It causes a lethal disease called myxomatosis in European rabbits but cannot sustain any detectable infection in nonlagomorphs. Vaccinia virus is a prototypal orthopoxvirus that was used as a vaccine to eradicate smallpox. Myxoma virus is nonpathogenic in mice, whereas systemic infection with vaccinia virus can be lethal even in immunocompetent mice. Plasmacytoid dendritic cells (pDCs) are potent type I interferon (IFN)-producing cells that play important roles in antiviral innate immunity. How poxviruses are sensed by pDCs to induce type I IFN production is not well understood. Here we report that infection of primary murine pDCs with myxoma virus, but not with vaccinia virus, induces IFN-\u03b1, IFN-\u03b2, tumor necrosis factor (TNF), and interleukin-12p70 (IL-12p70) production. Using pDCs derived from genetic knockout mice, we show that the myxoma virus-induced innate immune response requires the endosomal DNA sensor TLR9 and its adaptor MyD88, transcription factors IRF5 and IRF7, and the type I IFN positive-feedback loop mediated by IFNAR1. It is independent of the cytoplasmic RNA sensing pathway mediated by the mitochondrial adaptor molecule MAVS, the TLR3 adaptor TRIF, or the transcription factor IRF3. Using pharmacological inhibitors, we demonstrate that myxoma virus-induced type I IFN and IL-12p70 production in murine pDCs is also dependent on phosphatidylinositol 3-kinase (PI3K) and Akt. Furthermore, our results reveal that the N-terminal Z-DNA\/RNA binding domain of vaccinia virulence factor E3, which is missing in the orthologous M029 protein expressed by myxoma virus, plays an inhibitory role in poxvirus sensing and innate cytokine production by murine pDCs.\n          <\/jats:p>","DOI":"10.1128\/jvi.00104-11","type":"journal-article","created":{"date-parts":[[2011,8,11]],"date-time":"2011-08-11T04:01:06Z","timestamp":1313035266000},"page":"10814-10825","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Myxoma Virus Induces Type I Interferon Production in Murine Plasmacytoid Dendritic Cells via a TLR9\/MyD88-, IRF5\/IRF7-, and IFNAR-Dependent Pathway"],"prefix":"10.1128","volume":"85","author":[{"given":"Peihong","family":"Dai","sequence":"first","affiliation":[{"name":"Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Cao","sequence":"additional","affiliation":[{"name":"Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"},{"name":"Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Merghoub","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Avogadri","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvi","family":"Parikh","sequence":"additional","affiliation":[{"name":"Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"},{"name":"Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee-Mun","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Pitha","sequence":"additional","affiliation":[{"name":"Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masmudur M.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant","family":"McFadden","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Hu","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Signaling and Immune regulation, Hospital for Special Surgery, New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan N.","family":"Houghton","sequence":"additional","affiliation":[{"name":"Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"},{"name":"Weill Medical College of Cornell University, New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Shuman","sequence":"additional","affiliation":[{"name":"Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"},{"name":"Weill Medical College of Cornell University, New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Deng","sequence":"additional","affiliation":[{"name":"Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065"},{"name":"Weill Medical College of Cornell University, New York, New York 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