{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:34:20Z","timestamp":1790440460811,"version":"4.1.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"15","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"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":[[2007,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Kaposi's sarcoma-associated herpesvirus (KSHV\/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV\/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5\u2032 or 3\u2032 end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses.<\/jats:p>","DOI":"10.1128\/jvi.00411-07","type":"journal-article","created":{"date-parts":[[2007,5,23]],"date-time":"2007-05-23T21:01:06Z","timestamp":1179954066000},"page":"8225-8235","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing"],"prefix":"10.1128","volume":"81","author":[{"given":"Hyun Jin","family":"Kwun","sequence":"first","affiliation":[{"name":"Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzane Ramos","family":"da Silva","sequence":"additional","affiliation":[{"name":"Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213"},{"name":"Department of Pathology, Botucatu School of Medicine at Sao Paulo State University, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishita M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Blake","sequence":"additional","affiliation":[{"name":"Division of Medical Microbiology, School of Infection and Host Defense, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick S.","family":"Moore","sequence":"additional","affiliation":[{"name":"Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5414.641"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.7.3250-3258.2001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.1.294-301.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1120541"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910630107"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.211305198"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80397-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199505043321802"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8303295"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7997879"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1074883"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.717"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1627"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140129797"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.140217397"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.4.3154-3161.1999"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201258"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/47266"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.14.8019-8030.2003"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.16.10429-10441.2005"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201571"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199607253350403"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-925"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203489200"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.24.7650"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.56.1.328-332.1985"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307200200"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.22.11677-11687.2002"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.11.5300-5309.2000"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119804"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-918"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/375685a0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.23.12616"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01961-06"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.20.10320-10331.2002"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.13.7393-7400.2003"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.1.549-558.1996"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0397-287"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.24.11977-11982.2000"},{"key":"e_1_3_2_41_2","first-page":"2541","volume":"13","year":"1996","unstructured":"Parker, G. A., T. Crook, M. Bain, E. A. Sara, P. J. Farrell, and M. J. Allday. 1996. Epstein-Barr virus nuclear antigen (EBNA)3C is an immortalizing oncoprotein with similar properties to adenovirus E1A and papillomavirus E7. Oncogene13:2541-2549.","journal-title":"Oncogene"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5355"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/80459"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.8.5915-5921.1997"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.25.14862"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200524041"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.1005-1012.1998"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/35008096"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0898-939"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.4.1276.bloodjournal8641276"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.22.12566-12575.2004"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.4.1151.004k37_1151_1157"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.1.570-575.1996"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062508"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.22.2689"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.19.10348-10359.2004"},{"key":"e_1_3_2_57_2","first-page":"5","volume":"54","year":"1993","unstructured":"Wabinga, H. R., D. M. Parkin, F. Wabwire-Mangen, and J. Mugerwa. 1993. Cancer in Kampala, Uganda, in 1989-91: changes in incidence in the era of AIDS. Int. J. Cancer54:5-22.","journal-title":"Int. J. Cancer"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088902"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2006.05.012"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082420599"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00411-07","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00411-07","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T06:01:45Z","timestamp":1646460105000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00411-07"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":59,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1128\/JVI.00411-07"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00411-07","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8]]},"assertion":[{"value":"2007-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-05-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}