{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:42:21Z","timestamp":1784698941866,"version":"3.55.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MRC","award":["MR\/T016159\/1"],"award-info":[{"award-number":["MR\/T016159\/1"]}]},{"DOI":"10.13039\/501100002141","name":"Public Health England","doi-asserted-by":"crossref","award":["OB1"],"award-info":[{"award-number":["OB1"]}],"id":[{"id":"10.13039\/501100002141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["102174\/B\/13\/Z"],"award-info":[{"award-number":["102174\/B\/13\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"EU Horizon 2020","award":["H2020-MSCA-ITN-2016"],"award-info":[{"award-number":["H2020-MSCA-ITN-2016"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,3,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Lymphocytic choriomeningitis virus (LCMV) is a bisegmented negative-sense RNA virus classified within the\n                      <jats:italic>Arenaviridae<\/jats:italic>\n                      family of the\n                      <jats:italic>Bunyavirales<\/jats:italic>\n                      order. LCMV is associated with fatal disease in immunocompromized populations, and as the prototypical arenavirus, acts as a model for the many serious human pathogens within this group. Here, we examined the dependence of LCMV multiplication on cellular trafficking components using a recombinant LCMV expressing enhanced green fluorescent protein in conjunction with a curated siRNA library. The screen revealed a requirement for subunits of both the coat protein 1 (COPI) coatomer and adapter protein 4 (AP-4) complexes. By rescuing a recombinant LCMV harboring a FLAG-tagged glycoprotein (GP-1) envelope spike (rLCMV-GP1-FLAG), we showed infection resulted in marked co-localization of individual COPI and AP-4 components with both LCMV nucleoprotein (NP) and GP-1, consistent with their involvement in viral processes. To further investigate the role of both COPI and AP-4 complexes during LCMV infection, we utilized the ARF-I inhibitor brefeldin A (BFA) that prevents complex formation. Within a single 12-h cycle of virus multiplication, BFA pre-treatment caused no significant change in LCMV-specific RNA synthesis, alongside no significant change in LCMV NP expression, as measured by BFA time-of-addition experiments. In contrast, BFA addition resulted in a significant drop in released virus titers, approaching 50-fold over the same 12-h period, rising to over 600-fold over 24 h. Taken together, these findings suggest COPI and AP-4 complexes are important host cell factors required for the formation and release of infectious LCMV.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Arenaviruses are rodent-borne, segmented, negative-sense RNA viruses, with several members responsible for fatal human disease, with the prototypic member lymphocytic choriomeningitis virus (LCMV) being under-recognised as a pathogen capable of inflicting neurological infections with fatal outcome. A detailed understanding of how arenaviruses subvert host cell processes to complete their multiplication cycle is incomplete. Here, using a combination of gene ablation and pharmacological inhibition techniques, we showed that host cellular COPI and AP-4 complexes, with native roles in cellular vesicular transport, were required for efficient LCMV growth. We further showed these complexes acted on late stages of the multiplication cycle, post-gene expression, with a significant impact on infectious virus egress. Collectively, our findings improve the understanding of arenaviruses host-pathogen interactions and reveal critical cellular trafficking pathways required during infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.02006-23","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T08:32:32Z","timestamp":1707467552000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Lymphocytic choriomeningitis arenavirus requires cellular COPI and AP-4 complexes for efficient virion production"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1152-5763","authenticated-orcid":false,"given":"Owen","family":"Byford","sequence":"first","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom"},{"name":"Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia B.","family":"Shaw","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom"},{"name":"Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiu Nam","family":"Tse","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom"},{"name":"Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor J. 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