{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T23:36:41Z","timestamp":1781134601880,"version":"3.54.1"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2013,6,15]],"date-time":"2013-06-15T00:00:00Z","timestamp":1371254400000},"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":[[2013,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Several arenaviruses are responsible for causing viral hemorrhagic fevers (VHF) in humans. Lassa virus (LASV), the causative agent of Lassa fever, is a biosafety level 4 (BSL4) pathogen that requires handling in BSL4 facilities. In contrast, the Pichinde arenavirus (PICV) is a BSL2 pathogen that can cause hemorrhagic fever-like symptoms in guinea pigs that resemble those observed in human Lassa fever. Comparative sequence analysis of the avirulent P2 strain of PICV and the virulent P18 strain shows a high degree of sequence homology in the bisegmented genome between the two strains despite the polarized clinical outcomes noted for the infected animals. Using reverse genetics systems that we have recently developed, we have mapped the sequence changes in the large (L) segment of the PICV genome that are responsible for the heightened virulence phenotype of the P18 strain. By monitoring the degree of disease severity and lethality caused by the different mutant viruses, we have identified specific residues located within the viral L polymerase gene encoded on the L segment essential for mediating disease pathogenesis. Through quantitative reverse transcription-PCR (RT-PCR) analysis, we have confirmed that the same set of residues is responsible for the increased viral replicative potential of the P18 strain and its heightened disease severity\n            <jats:italic>in vivo<\/jats:italic>\n            . Our laboratory findings serve to reinforce field observations that a high level of viremia often correlates with severe disease outcomes in LASV-infected patients.\n          <\/jats:p>","DOI":"10.1128\/jvi.00044-13","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T06:59:59Z","timestamp":1365058799000},"page":"6635-6643","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Identification of Virulence Determinants within the L Genomic Segment of the Pichinde Arenavirus"],"prefix":"10.1128","volume":"87","author":[{"given":"Lisa","family":"McLay","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiyun","family":"Lan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aftab","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinh","family":"Ly","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA"},{"name":"Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1635","volume-title":"Fields virology","author":"Buchmeier M","year":"2001","unstructured":"BuchmeierM BowenM PetersC. 2001. 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