{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T05:56:57Z","timestamp":1782885417414,"version":"3.54.5"},"reference-count":71,"publisher":"American Society for Microbiology","issue":"24","license":[{"start":{"date-parts":[[2011,12,15]],"date-time":"2011-12-15T00:00:00Z","timestamp":1323907200000},"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":[[2011,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Human cytomegalovirus is a ubiquitous herpesvirus that establishes lifelong latent infection. Changes in immune homeostasis induce the reactivation of lytic infection, which is mostly inapparent in healthy individuals but often causes overt disease in immunocompromised hosts. Based on discrepant tumor necrosis factor receptor 1 surface disposition between human cytomegalovirus AD169 variants differing in the UL<jats:italic>b<\/jats:italic>\u2032 region, we identified the latency-associated gene product pUL138, which also is expressed during productive infection, as a selective potentiator of tumor necrosis factor receptor 1, one of the key receptors of innate immunity. Ectopically expressed pUL138 coprecipitated with tumor necrosis factor receptor 1, extended the protein half-life, and enhanced its signaling responses, thus leading to tumor necrosis factor receptor 1 hyperresponsiveness. Conversely, the targeted deletion of<jats:italic>UL138<\/jats:italic>from the human cytomegaloviral genome strongly reduced tumor necrosis factor receptor 1 surface densities of infected cells. Remarkably, the comparison of<jats:italic>UL138<\/jats:italic>deficiency to UL<jats:italic>b<\/jats:italic>\u2032 deficiency revealed the presence of further positive modulators of tumor necrosis factor alpha signal transduction encoded within the human cytomegalovirus UL<jats:italic>b<\/jats:italic>\u2032 region, identifying this region as a hub for multilayered tumor necrosis factor alpha signaling regulation.<\/jats:p>","DOI":"10.1128\/jvi.06005-11","type":"journal-article","created":{"date-parts":[[2011,10,6]],"date-time":"2011-10-06T05:58:09Z","timestamp":1317880689000},"page":"13260-13270","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":89,"title":["The Cytomegaloviral Protein pUL138 Acts as Potentiator of Tumor Necrosis Factor (TNF) Receptor 1 Surface Density To Enhance UL<i>b<\/i>\u2032-Encoded Modulation of TNF-\u03b1 Signaling"],"prefix":"10.1128","volume":"85","author":[{"given":"Vu Thuy Khanh","family":"Le","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Virologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Trilling","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Virologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Hengel","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Virologie, Heinrich-Heine-Universit\u00e4t D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.17.8596-8608.2002"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.12.7007-7016.2003"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.17.11022-11034.2005"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008218200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.8320-8329.1999"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.013250-0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59421-2_16"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.1.78-83.1996"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1071924"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.10.5815"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.21.13606-13617.2005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82001-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-008-0278-4"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.9.4498-4507.2004"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.79888-0"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.23.13113-13121.2004"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199409000-00007"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806113382407"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.8.4114-4123.1991"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.4049\/jimmunol.145.9.3080","article-title":"The adenovirus E3-14.7K protein is a general inhibitor of tumor necrosis factor-mediated cytolysis","volume":"145","author":"Gooding L. R.","year":"1990","unstructured":"GoodingL. R. SofolaI. O. TollefsonA. E. DuerksenhughesP. WoldW. S. M.. 1990. The adenovirus E3-14.7K protein is a general inhibitor of tumor necrosis factor-mediated cytolysis. J. Immunol. 145:3080\u20133086.","journal-title":"J. Immunol."},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-070078"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00855-10"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(06)52002-9"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.18.9551-9555.2002"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.18.10023-10033.2004"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014509107"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-76-12-2987"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(67)90307-5"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.10.4814-4822.2001"},{"key":"e_1_3_3_31_2","first-page":"309","article-title":"Antiviral effects of recombinant human tumor necrosis factor","volume":"6","author":"Ito M.","year":"1987","unstructured":"ItoM. OmalleyJ. A.. 1987. Antiviral effects of recombinant human tumor necrosis factor. Lymphokine Res. 6:309\u2013318.","journal-title":"Lymphokine Res."},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00060-06"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.3.1440-1447.2004"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.621"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.4180102"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.54.070185.003215"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1086\/520307"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01610"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.2008\/001669-0"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.3.1042"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/08830180490265556"},{"key":"e_1_3_3_42_2","first-page":"537","article-title":"Regulation of the immune system by NF-kappa B and I kappa B","volume":"35","author":"Liou H. C","year":"2002","unstructured":"LiouH. C. 2002. Regulation of the immune system by NF-kappa B and I kappa B. J. Biochem. Mol. Biol. 35:537\u2013546.","journal-title":"J. Biochem. Mol. Biol."},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-75-1-101"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(01)00262-5"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.19.9683"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01168-06"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2136652100"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199705270-00007"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01989-08"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601287"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.18.10125-10130.2003"},{"key":"e_1_3_3_52_2","first-page":"333","article-title":"Cytomegalovirus immune evasion","volume":"325","author":"Powers C.","year":"2008","unstructured":"PowersC. DeFilippisV. MalouliD. FruhK.. 2008. Cytomegalovirus immune evasion. Curr. Top. Microbiol. Immunol. 325:333\u2013359.","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1143"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0367"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1001-9294(09)60071-7"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408994102"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23771"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8299-8306.1997"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.1.326-340.2005"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.83286-0"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-80-11-2867"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)80014-3"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.1.172-181.1995"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01195-06"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/33712"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.19.8875-8887.2001"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02042-08"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-010-0283-0"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020811"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401189"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1006\/smvy.1998.0155"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.9.5391-5400.1995"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.06005-11","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.06005-11","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,10]],"date-time":"2023-06-10T08:22:34Z","timestamp":1686385354000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.06005-11"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,15]]},"references-count":71,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2011,12,15]]}},"alternative-id":["10.1128\/JVI.06005-11"],"URL":"https:\/\/doi.org\/10.1128\/jvi.06005-11","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,15]]},"assertion":[{"value":"2011-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-09-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-11-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}