{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:57:42Z","timestamp":1790470662127,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"23","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"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":[[2015,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hemorrhagic fever arenaviruses (HFA) pose important public health problems in regions where they are endemic. Thus, Lassa virus (LASV) infects several hundred thousand individuals yearly in West Africa, causing a large number of Lassa fever cases associated with high morbidity and mortality. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. The Mopeia virus (MOPV)\/LASV reassortant (ML29) is a LASV candidate live-attenuated vaccine (LAV) that has shown promising results in animal models. Nevertheless, the mechanism of ML29 attenuation remains unknown, which raises concerns about the phenotypic stability of ML29 in response to additional mutations. Development of LAVs based on well-defined molecular mechanisms of attenuation will represent a major step in combatting HFA. We used the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) to develop a general molecular strategy for arenavirus attenuation. Our approach involved replacement of the noncoding intergenic region (IGR) of the L genome segment with the IGR of the S genome segment to generate a recombinant LCMV, rLCMV(IGR\/S-S), that was highly attenuated\n            <jats:italic>in vivo<\/jats:italic>\n            but induced protection against a lethal challenge with wild-type LCMV. Attenuation of rLCMV(IGR\/S-S) was associated with a stable reorganization of the control of viral gene expression. This strategy can facilitate the rapid development of LAVs with the antigenic composition of the parental HFA and a mechanism of attenuation that minimizes concerns about increased virulence that could be caused by genetic changes in the LAV.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Hemorrhagic fever arenaviruses (HFA) cause high morbidity and mortality, and pose important public health problems in the regions where they are endemic. Implementation of live-attenuated vaccines (LAV) will represent a major step in combatting HFA. Here we have used the prototypic arenavirus LCMV to document a general molecular strategy for arenavirus attenuation that can facilitate the rapid development of safe and effective, as well as stable, LAV to combat HFA.\n          <\/jats:p>","DOI":"10.1128\/jvi.02075-15","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T02:37:56Z","timestamp":1443062276000},"page":"12166-12177","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["General Molecular Strategy for Development of Arenavirus Live-Attenuated Vaccines"],"prefix":"10.1128","volume":"89","author":[{"given":"Masaharu","family":"Iwasaki","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhi","family":"Ngo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Cubitt","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Teijaro","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"de la Torre","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2005.05.001"},{"key":"e_1_3_2_3_2","first-page":"1791","volume-title":"Fields virology","author":"Buchmeier MJ","year":"2007","unstructured":"Buchmeier MJ, Peters CJ, de la Torre JC. 2007. Arenaviridae: the viruses and their replication, p 1791\u20131851. In Knipe DM, Howley PM (ed), Fields virology, 5th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1142"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7426.1271"},{"key":"e_1_3_2_6_2","first-page":"865","article-title":"Emerg infectious diseases and risk to the traveler","volume":"83","author":"Freedman DO","year":"1999","unstructured":"Freedman DO, Woodall J. 1999. Emerg infectious diseases and risk to the traveler. Med Clin North Am 83:865\u2013883.","journal-title":"Med Clin North Am"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/322620"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000455"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1510.090211"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2002.126297"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa053240"},{"key":"e_1_3_2_12_2","first-page":"486","article-title":"Lymphocytic choriomeningitis virus. A neglected pathogen of man","volume":"116","author":"Jahrling PB","year":"1992","unstructured":"Jahrling PB, Peters CJ. 1992. Lymphocytic choriomeningitis virus. A neglected pathogen of man. Arch Pathol Lab Med 116:486\u2013488.","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073785"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp068021"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.18.2391"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003212"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/657315"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(02)58004-0"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1612.100994"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.04.007"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-10-52"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.5.2621-2627.1993"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2133782100"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.19.10700-10705.2003"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.7.4519-4526.2005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.8.3470-3477.2000"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.12.6393-6397.2002"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01012-09"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900088106"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0600652103"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.01.012"},{"key":"e_1_3_2_32_2","first-page":"6","article-title":"Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24 well plates","volume":"10","author":"Battegay M","year":"1993","unstructured":"Battegay M. 1993. Quantification of lymphocytic choriomeningitis virus with an immunological focus assay in 24 well plates. ALTEX 10:6\u201314.","journal-title":"ALTEX"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.2.1184-1194.2003"},{"key":"e_1_3_2_34_2","first-page":"1831","article-title":"Lymphocytic choriomeningitis virus: pathogenesis of acute central nervous system disease","volume":"30","author":"Cole GA","year":"1971","unstructured":"Cole GA, Gilden DH, Monjan AA, Nathanson N. 1971. Lymphocytic choriomeningitis virus: pathogenesis of acute central nervous system disease. Fed Proc 30:1831\u20131841.","journal-title":"Fed Proc"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4911-4927.2003"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00555-06"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.3.1370-1376.1992"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.186262"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00856-11"},{"key":"e_1_3_2_40_2","first-page":"41","article-title":"Heterogeneity and stability characteristics of Candid 1 attenuated strain of Junin virus","volume":"37","author":"Contigiani M","year":"1993","unstructured":"Contigiani M, Medeot S, Diaz G. 1993. Heterogeneity and stability characteristics of Candid 1 attenuated strain of Junin virus. Acta Virol 37:41\u201346.","journal-title":"Acta Virol"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02201-08"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01270-10"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3259-3272.2006"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03401-14"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411290111"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00738-06"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307473110"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(90)90053-T"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02075-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02075-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:04:34Z","timestamp":1646489074000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02075-15"}},"subtitle":[],"editor":[{"given":"T. S.","family":"Dermody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,12]]},"references-count":47,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2015,12]]}},"alternative-id":["10.1128\/JVI.02075-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02075-15","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12]]},"assertion":[{"value":"2015-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-11-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}