PMID- 22438548 OWN - NLM STAT- MEDLINE DCOM- 20120618 LR - 20240504 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 86 IP - 10 DP - 2012 May TI - The double-stranded RNA bluetongue virus induces type I interferon in plasmacytoid dendritic cells via a MYD88-dependent TLR7/8-independent signaling pathway. PG - 5817-28 LID - 10.1128/JVI.06716-11 [doi] AB - Dendritic cells (DCs), especially plasmacytoid DCs (pDCs), produce large amounts of alpha/beta interferon (IFN-alpha/beta) upon infection with DNA or RNA viruses, which has impacts on the physiopathology of the viral infections and on the quality of the adaptive immunity. However, little is known about the IFN-alpha/beta production by DCs during infections by double-stranded RNA (dsRNA) viruses. We present here novel information about the production of IFN-alpha/beta induced by bluetongue virus (BTV), a vector-borne dsRNA Orbivirus of ruminants, in sheep primary DCs. We found that BTV induced IFN-alpha/beta in skin lymph and in blood in vivo. Although BTV replicated in a substantial fraction of the conventional DCs (cDCs) and pDCs in vitro, only pDCs responded to BTV by producing a significant amount of IFN-alpha/beta. BTV replication in pDCs was not mandatory for IFN-alpha/beta production since it was still induced by UV-inactivated BTV (UV-BTV). Other inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-12p40, were also induced by UV-BTV in primary pDCs. The induction of IFN-alpha/beta required endo-/lysosomal acidification and maturation. However, despite being an RNA virus, UV-BTV did not signal through Toll-like receptor 7 (TLR7) for IFN-alpha/beta induction. In contrast, pathways involving the MyD88 adaptor and kinases dsRNA-activated protein kinase (PKR) and stress-activated protein kinase (SAPK)/Jun N-terminal protein kinase (JNK) were implicated. This work highlights the importance of pDCs for the production of innate immunity cytokines induced by a dsRNA virus, and it shows that a dsRNA virus can induce IFN-alpha/beta in pDCs via a novel TLR-independent and Myd88-dependent pathway. These findings have implications for the design of efficient vaccines against dsRNA viruses. FAU - Ruscanu, Suzana AU - Ruscanu S AD - Virologie et Immunologie Moleculaires, UR892 INRA, Jouy-en-Josas, France. FAU - Pascale, Florentina AU - Pascale F FAU - Bourge, Mickael AU - Bourge M FAU - Hemati, Behzad AU - Hemati B FAU - Elhmouzi-Younes, Jamila AU - Elhmouzi-Younes J FAU - Urien, Celine AU - Urien C FAU - Bonneau, Michel AU - Bonneau M FAU - Takamatsu, Haru AU - Takamatsu H FAU - Hope, Jayne AU - Hope J FAU - Mertens, Peter AU - Mertens P FAU - Meyer, Gilles AU - Meyer G FAU - Stewart, Meredith AU - Stewart M FAU - Roy, Polly AU - Roy P FAU - Meurs, Eliane F AU - Meurs EF FAU - Dabo, Stephanie AU - Dabo S FAU - Zientara, Stephan AU - Zientara S FAU - Breard, Emmanuel AU - Breard E FAU - Sailleau, Corinne AU - Sailleau C FAU - Chauveau, Emilie AU - Chauveau E FAU - Vitour, Damien AU - Vitour D FAU - Charley, Bernard AU - Charley B FAU - Schwartz-Cornil, Isabelle AU - Schwartz-Cornil I LA - eng GR - BB/F00852X/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BBS/E/I/00001441/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BBS/E/I/00001709/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120321 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Cytokines) RN - 0 (Interferon Type I) RN - 0 (Membrane Glycoproteins) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Receptors, Interleukin-1) RN - 0 (TIRAP protein, human) RN - 0 (Toll-Like Receptor 7) RN - 0 (Toll-Like Receptor 8) SB - IM MH - Animals MH - Bluetongue/genetics/*immunology/virology MH - Bluetongue virus/genetics/*immunology/physiology MH - Cells, Cultured MH - Cytokines/genetics/immunology MH - Dendritic Cells/*immunology/virology MH - Female MH - Immunity, Innate MH - Interferon Type I/genetics/*immunology MH - Membrane Glycoproteins MH - Myeloid Differentiation Factor 88/genetics/*immunology MH - Receptors, Interleukin-1 MH - Sheep/immunology/virology MH - Signal Transduction MH - Toll-Like Receptor 7/genetics/*immunology MH - Toll-Like Receptor 8/genetics/*immunology PMC - PMC3347300 EDAT- 2012/03/23 06:00 MHDA- 2012/06/19 06:00 PMCR- 2012/11/01 CRDT- 2012/03/23 06:00 PHST- 2012/03/23 06:00 [entrez] PHST- 2012/03/23 06:00 [pubmed] PHST- 2012/06/19 06:00 [medline] PHST- 2012/11/01 00:00 [pmc-release] AID - JVI.06716-11 [pii] AID - 06716-11 [pii] AID - 10.1128/JVI.06716-11 [doi] PST - ppublish SO - J Virol. 2012 May;86(10):5817-28. doi: 10.1128/JVI.06716-11. Epub 2012 Mar 21.