{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:28:43Z","timestamp":1786541323330,"version":"build-2736575974"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T00:00:00Z","timestamp":1301616000000},"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":[[2011,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The emergence of zoonotic orthopoxvirus infections and the threat of possible intentional release of pathogenic orthopoxviruses have stimulated renewed interest in understanding orthopoxvirus infections and the resulting diseases. Ectromelia virus (ECTV), the causative agent of mousepox, offers an excellent model system to study an orthopoxvirus infection in its natural host. Here, we investigated the role of the vaccinia virus ortholog N1L in ECTV infection. Respiratory infection of mice with an N1L deletion mutant virus (ECTV\u0394N1L) demonstrated profound attenuation of the mutant virus, confirming N1 as an orthopoxvirus virulence factor. Upon analysis of virus dissemination<jats:italic>in vivo<\/jats:italic>, we observed a striking deficiency of ECTV\u0394N1L spreading from the lungs to the livers or spleens of infected mice. Investigating the immunological mechanism controlling ECTV\u0394N1L infection, we found the attenuated phenotype to be unaltered in mice deficient in Toll-like receptor (TLR) or RIG-I-like RNA helicase (RLH) signaling as well as in those missing the type I interferon receptor or lacking B cells. However, in RAG-1<jats:sup>\u2212\/\u2212<\/jats:sup>mice lacking mature B and T cells, ECTV\u0394N1L regained virulence, as shown by increasing morbidity and virus spread to the liver and spleen. Moreover, T cell depletion experiments revealed that ECTV\u0394N1L attenuation was reversed only by removing both CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells, so the presence of either cell subset was still sufficient to control the infection. Thus, the orthopoxvirus virulence factor N1 may allow efficient ECTV infection in mice by interfering with host T cell function.<\/jats:p>","DOI":"10.1128\/jvi.01191-10","type":"journal-article","created":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T02:25:18Z","timestamp":1296095118000},"page":"3557-3569","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["N1L Is an Ectromelia Virus Virulence Factor and Essential for<i>In Vivo<\/i>Spread upon Respiratory Infection"],"prefix":"10.1128","volume":"85","author":[{"given":"Meike S.","family":"Gratz","sequence":"first","affiliation":[{"name":"Paul-Ehrlich-Institut, Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Suezer","sequence":"additional","affiliation":[{"name":"Paul-Ehrlich-Institut, Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Kremer","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universita\u0308t Mu\u0308nchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asisa","family":"Volz","sequence":"additional","affiliation":[{"name":"Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universita\u0308t Mu\u0308nchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monir","family":"Majzoub","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Ludwig-Maximilians-Universita\u0308t Mu\u0308nchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay-Martin","family":"Hanschmann","sequence":"additional","affiliation":[{"name":"Paul-Ehrlich-Institut, Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kalinke","sequence":"additional","affiliation":[{"name":"Paul-Ehrlich-Institut, Langen, Germany"},{"name":"TWINCORE, Center for Experimental and Clinical Infection Research, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Schwantes","sequence":"additional","affiliation":[{"name":"Paul-Ehrlich-Institut, Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Sutter","sequence":"additional","affiliation":[{"name":"Paul-Ehrlich-Institut, Langen, Germany"},{"name":"Institute for Infectious Diseases and Zoonoses, Ludwig-Maximilians-Universita\u0308t Mu\u0308nchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri980"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.062454707"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-8-1965"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00892-10"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02202-09"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.3246"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.160027697"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(88)90424-6"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/315190"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020025"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-81-4-1087"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00116-06"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(99)00135-5"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82772-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008506"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.907"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00856-9"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400567200"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2009.08.026"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.81090-0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.6.3108-3111.1990"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040030"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700600402"},{"key":"e_1_3_2_25_2","unstructured":"Smallpox and its eradication. 1988"},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4049\/jimmunol.63.4.341","volume":"63","year":"1949","unstructured":"Fenner, F. 1949. Mouse-pox (infectious ectromelia of mice): a review. J. Immunol. 63:341-373.","journal-title":"J. Immunol."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.034"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401718"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206036"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90644-6"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.19565-0"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07725"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(89)90359-4"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.2008\/004119-0"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01313742"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.11.6093-6100.2003"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.11.002"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.12.8301-8309.1996"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.7.4214-4226.1993"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2112266"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(89)90627-2"},{"key":"e_1_3_2_42_2","first-page":"101","volume":"269","year":"2004","unstructured":"Kotwal, G. J., and M.-R. Abrahams. 2004. Growing poxviruses and determining virus titer. Methods Mol. Biol. 269:101-112.","journal-title":"Methods Mol. Biol."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060792"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.6.2770-2779.2004"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3786"},{"key":"e_1_3_2_46_2","first-page":"15","volume":"269","year":"2004","unstructured":"Lorenzo, M. M., I. Galindo, and R. Blasco. 2004. Construction and isolation of recombinant vaccinia virus using genetic markers. Methods Mol. Biol. 269:15-30.","journal-title":"Methods Mol. Biol."},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.5858\/2000-124-0362-AMMOAT"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1058867"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003323"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1099"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90030-G"},{"key":"e_1_3_2_52_2","first-page":"877","volume":"48","year":"1966","unstructured":"Montasir, M., E. R. Rabin, and C. A. Phillips. 1966. Vaccinia pneumonia in mice: a light and electron microscopic and viral assay study. Am. J. Pathol. 48:877-895.","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8009221"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00115-06"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1086\/595565"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02061-06"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1864"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005769107"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33940"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141049"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1014"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1177\/095632020101200105"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(98)00125-4"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1997.tb01012.x"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8460-8471.2000"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.2144\/03344bm02"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100033"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06013"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100100"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1594"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01190-07"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801295105"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235583100"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/344742a0"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01191-10","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01191-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T13:25:23Z","timestamp":1712150723000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01191-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,4]]},"references-count":74,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2011,4]]}},"alternative-id":["10.1128\/JVI.01191-10"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01191-10","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4]]},"assertion":[{"value":"2010-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-12-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-03-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}