{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:39:19Z","timestamp":1793129959079,"version":"4.5.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI048088"],"award-info":[{"award-number":["AI048088"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Indian Health Board","award":["CA147922"],"award-info":[{"award-number":["CA147922"]}],"id":[{"id":"https:\/\/ror.org\/02698x773","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM094198"],"award-info":[{"award-number":["GM094198"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      During the intracellular replication cycle of West Nile virus (WNV), genome RNA synthesis is initially inefficient but increases exponentially as viral replication complexes are sequestered in invaginations in the endoplasmic reticulum. In this study, we investigated the functional role of the cellular protein TIAR (T-cell intracellular antigen-related protein) in the transcription of WNV genome RNA. Close colocalization of cytoplasmic TIAR with viral double-stranded RNA was detected by a proximity ligation assay in WNV-infected cells. TIAR binds specifically to the WNV 3\u02b9(\u2212) SL but not to the complementary WNV 5\u02b9(+) SL in\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      RNA binding assays. Only the 3\u2032 end of the WNV minus-strand RNA was enriched by immunoprecipitation of infected cell lysates with anti-TIAR antibody. Stable overexpression of TIAR in clonal A549 cells increased the ratio of intracellular viral plus-strand to minus-strand RNA in a dose-dependent manner. TIAR contains three RNA recognition motifs (RRMs). Biophysical data indicated that only RRM2 directly contacts RNA and that up to three TIAR molecules can bind cooperatively to the WNV 3\u02b9(\u2212) SL RNA. These data provide additional evidence that TIAR functions as a proviral host factor facilitating exponential amplification of WNV genome production in infected cells.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        West Nile virus (WNV) is a mosquito-borne orthoflavivirus associated with increasing global human disease incidence. The molecular mechanisms underlying viral replication are not fully understood. In early stages of infection, viral genome transcription is inefficient; however, in late stages, viral genome transcription increases exponentially. T-cell intracellular antigen-related (TIAR) protein is a cellular protein that has been shown to interact with the 3\u2032 end of the WNV negative-sense antigenomic RNA. We obtained data showing colocalization of cellular TIAR with viral replication complexes in infected cells and an increased ratio of intracellular genomic to antigenomic viral RNA in TIAR-overexpressing cells, and confirmed preferential binding of TIAR to the 3\u2032 end of the WNV antigenome both\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and in infected cell extracts. We also demonstrated that multiple TIAR proteins can bind cooperatively to the WNV 3\u2032(\u2212) stem-loop RNA. These data provide supporting evidence for a model of TIAR-mediated rapid initiation of nascent genome RNA synthesis in infected cells.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01947-26","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:02:02Z","timestamp":1788872522000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["The cellular protein TIAR mediates rapid initiation of West Nile virus genome RNA synthesis"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-4811","authenticated-orcid":false,"given":"Jessica L.","family":"Siemer","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-7643","authenticated-orcid":false,"given":"Hsuan","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Cui","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeenah","family":"Jung","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Santangelo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus W.","family":"Germann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Georgia State University","place":["Atlanta, USA"]},{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4868-175X","authenticated-orcid":true,"given":"Margo A.","family":"Brinton","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-137-3-200208060-00009"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb02693.x"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1144"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1466252307001430"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1108.050289a"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12211"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70030-3"},{"key":"e_1_3_7_9_2","first-page":"1101","volume-title":"Fields virology","author":"Lindenbach B","year":"2007","unstructured":"Lindenbach B, Thiel HJ, Rice CM. 2007. 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