{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:05:38Z","timestamp":1790867138503,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"22","license":[{"start":{"date-parts":[[2007,11,15]],"date-time":"2007-11-15T00:00:00Z","timestamp":1195084800000},"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":[[2007,11,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus strain undergoing clinical evaluation as a replication-deficient vaccine vector against various infections and tumor diseases. To analyze the basis of its high immunogenicity, we investigated the mechanism of how MVA induces type I interferon (IFN) responses. MVA stimulation of bone marrow-derived dendritic cells (DC) showed that plasmacytoid DC were main alpha IFN (IFN-\u03b1) producers that were triggered independently of productive infection, viral replication, or intermediate and late viral gene expression. Increased IFN-\u03b1 levels were induced upon treatment with mildly UV-irradiated MVA, suggesting that a virus-encoded immune modulator(s) interfered with the host cytokine response. Mice devoid of Toll-like receptor 9 (TLR9), the receptor for double-stranded DNA, mounted normal IFN-\u03b1 responses upon MVA treatment. Furthermore, mice devoid of the adaptors of TLR signaling MyD88 and TRIF and mice deficient in protein kinase R (PKR) showed IFN-\u03b1 responses that were only slightly reduced compared to those of wild-type mice. MVA-induced IFN-\u03b1 responses were critically dependent on autocrine\/paracrine triggering of the IFN-\u03b1\/\u03b2 receptor and were independent of IFN-\u03b2, thus involving \u201cone-half\u201d of a positive-feedback loop. In conclusion, MVA-mediated type I IFN secretion was primarily triggered by non-TLR molecules, was independent of virus propagation, and critically involved IFN feedback stimulation. These data provide the basis to further improve MVA as a vaccine vector.<\/jats:p>","DOI":"10.1128\/jvi.01190-07","type":"journal-article","created":{"date-parts":[[2007,9,14]],"date-time":"2007-09-14T00:54:02Z","timestamp":1189731242000},"page":"12102-12110","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":107,"title":["Modified Vaccinia Virus Ankara Induces Toll-Like Receptor-Independent Type I Interferon Responses"],"prefix":"10.1128","volume":"81","author":[{"given":"Zoe","family":"Waibler","sequence":"first","affiliation":[{"name":"Division of Immunology, Paul-Ehrlich-Institut, D-63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Anzaghe","sequence":"additional","affiliation":[{"name":"Division of Immunology, Paul-Ehrlich-Institut, D-63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Division of Virology, Paul-Ehrlich-Institut, D-63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuo","family":"Akira","sequence":"additional","affiliation":[{"name":"Department of Host Defense, Research Institute of Microbial Diseases, Osaka University, Suita-ku, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Weiss","sequence":"additional","affiliation":[{"name":"Molekulare Immunologie, Helmholtz Zentrum fu\u0308r Infektionsforschung, D-38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Sutter","sequence":"additional","affiliation":[{"name":"Division of Virology, Paul-Ehrlich-Institut, D-63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"Division of Immunology, Paul-Ehrlich-Institut, D-63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80596-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1391"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.8.4633-4639.1995"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"624","DOI":"10.4049\/jimmunol.160.2.624","volume":"160","year":"1998","unstructured":"Alcami, A., J. A. Symons, P. D. Collins, T. J. Williams, and G. L. Smith. 1998. Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. J. Immunol.160:624-633.","journal-title":"J. Immunol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9123"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00014-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011666"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.04.005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-5-1159"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.160027697"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2427(94)05357-X"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8845"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.27.15974"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1141"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.7.3404-3409.2000"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093616"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01783"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-2-347"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.79998-0"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70086-7"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6304"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603082103"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.8423"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021652"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/35047123"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.6.3741-3752.1996"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403555101"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01889"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0406933101"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1539"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1282"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.04.010"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1118"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.06.007"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2674"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030162"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.2.383"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-72-5-1031"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01265-06"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8009221"},{"key":"e_1_3_2_42_2","first-page":"131","volume":"40","year":"1993","unstructured":"Munz, E., S. Linckh, I. C. Renner-Muller, and M. Reimann. 1993. The effectiveness of immunization with vaccinia virus type \u201cMVA\u201d against an infection with cowpox virus type \u201cOPV 85\u201d in rabbits. Zentbl. Veterinarmed. B40:131-140.","journal-title":"Zentbl. Veterinarmed. B"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00751-06"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.1090"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.02.028"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0462"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041442"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.12.003"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10847"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(94)90341-7"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.8.4792-4796.1995"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1995.tb00090.x"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2001.89.re2"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1995.tb00300.x"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-027136"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01190-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01190-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,14]],"date-time":"2023-05-14T04:12:06Z","timestamp":1684037526000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01190-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11,15]]},"references-count":54,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2007,11,15]]}},"alternative-id":["10.1128\/JVI.01190-07"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01190-07","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11,15]]},"assertion":[{"value":"2007-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-11-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}