{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:29:32Z","timestamp":1789086572473,"version":"build-2803163510"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24KJ1211"],"award-info":[{"award-number":["24KJ1211"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP243fa627005"],"award-info":[{"award-number":["JP243fa627005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23wm0125008"],"award-info":[{"award-number":["JP23wm0125008"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The rabies virus large (L) protein interacts with its cofactor phosphoprotein (P protein) to function as an RNA-dependent RNA polymerase (RdRp). The C-terminal domain (CTD) of the L protein plays a critical role in P protein binding. We previously reported that the highly conserved NPYNE sequence in the hydrophilic region of the CTD (positions 1929\u20131933 of the L protein [L1929\u20131933]) is important for both P protein binding and RdRp function. To elucidate the functional role of the CTD in detail, we examined the importance of each of the hydrophilic residues in the\n              <jats:underline>N<\/jats:underline>\n              PY\n              <jats:underline>NE<\/jats:underline>\n              sequence (underlined). A rabies virus mutant with Ala substitutions in these hydrophilic residues showed low replication capacity. Comprehensive analyses of a revertant of the mutant virus and a series of L protein mutants revealed that Asn at L1929 is crucial for both P protein binding and RdRp function. Analyses of the L protein mutants also showed that Asn at L1932 and Glu at L1933 have roles in RdRp function and P protein binding, respectively. Furthermore, we demonstrated that the NPYNE sequence is essential for stabilizing the L protein through the L-P interaction. In a previously determined L protein structure, all of the hydrophilic residues in the NPYNE sequence form the first \u03b1-helix in the CTD. Therefore, our findings indicate that this helix is important for P protein-binding ability, RdRp function, and stabilization of the L protein, thereby contributing to efficient viral replication.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Although RNA-dependent RNA polymerase of rhabdoviruses, which is composed of the large (L) protein and its cofactor phosphoprotein (P protein), has a high potential as a target for therapeutics against the viruses, the relationship between the structure and molecular functions is poorly understood. In this study, we functionally examined the C-terminal domain (CTD) of the rabies virus L protein as a model for the rhabdovirus L protein. We showed that the first \u03b1-helix in the CTD is important for the P protein-binding ability, RdRp function, and stability of the L protein. Since in the L-P complex structure, this helix does not form an interface with the P protein, we provide here the first evidence of an indirect contribution of the L protein CTD to the L-P interaction in rhabdoviruses. The findings in this study will be useful for developing therapeutics targeting the L-P interaction.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.02082-24","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T13:02:21Z","timestamp":1741698141000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Functional dissection of the C-terminal domain of rabies virus RNA polymerase L protein"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4046-0829","authenticated-orcid":false,"given":"Fumiki","family":"Izumi","sequence":"first","affiliation":[{"name":"Joint Graduate School of Veterinary Sciences, Gifu University","place":["Gifu, Japan"]},{"name":"Research Fellow of Japan Society for the Promotion of Science (JSPS)","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiko","family":"Makino","sequence":"additional","affiliation":[{"name":"Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-2175","authenticated-orcid":true,"given":"Michihito","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University","place":["Sapporo, Japan"]},{"name":"Institute for Vaccine Research and Development (IVReD), Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"The United Graduate School of Veterinary Sciences, Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"The United Graduate School of Veterinary Sciences, Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4613-7232","authenticated-orcid":true,"given":"Yuji","family":"Fujii","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Sciences, Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misuzu","family":"Okajima","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Sciences, Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsunori","family":"Masatani","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Sciences, Gifu University","place":["Gifu, Japan"]},{"name":"Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University","place":["Gifu, Japan"]},{"name":"Center for One Medicine Innovative Translational Research (COMIT), Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Division of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Sawa","sequence":"additional","affiliation":[{"name":"Institute for Vaccine Research and Development (IVReD), Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0296-966X","authenticated-orcid":true,"given":"Naoto","family":"Ito","sequence":"additional","affiliation":[{"name":"Joint Graduate School of Veterinary Sciences, Gifu University","place":["Gifu, Japan"]},{"name":"Laboratory of Zoonotic Diseases, Faculty of Applied Biological Sciences, Gifu University","place":["Gifu, Japan"]},{"name":"Center for One Medicine Innovative Translational Research (COMIT), Gifu University","place":["Gifu, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003709"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16982-1"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2012.06.001"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2005.73.566"},{"key":"e_1_3_5_6_2","first-page":"395","article-title":"Chandipura virus encephalitis outbreak among children in Nagpur division, Maharashtra, 2007","volume":"132","author":"Gurav YK","year":"2010","unstructured":"Gurav YK, Tandale BV, Jadi RS, Gunjikar RS, Tikute SS, Jamgaonkar AV, Khadse RK, Jalgaonkar SV, Arankalle VA, Mishra AC. 2010. Chandipura virus encephalitis outbreak among children in Nagpur division, Maharashtra, 2007. Indian J Med Res 132:395\u2013399.","journal-title":"Indian J Med Res"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21041"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01861-0"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01490"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/v8050144"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/v11060504"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1058"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-49-1-181"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0263"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1918809117"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.12.024"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.014"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1759-1"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14246-3"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1919837117"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05271-2"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37012-y"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06608-1"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06867-y"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47470-7"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48389-9"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52701-y"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00175-20"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.018"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00826-17"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.3.1925-1930.1998"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00977-09"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2006.tb03767.x"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.03.061"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560070103"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3381086"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1013559107"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02180-20"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209147109"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1331"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1676"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03619-14"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00602-16"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02220-16"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.12.026"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002924"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(74)90237-1"},{"key":"e_1_3_5_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.2003.tb03424.x"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.71.9.6706-6713.1997"},{"key":"e_1_3_5_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02220-09"},{"key":"e_1_3_5_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1994.tb01806.x"},{"key":"e_1_3_5_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02132-13"},{"key":"e_1_3_5_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2021.05.002"},{"key":"e_1_3_5_54_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3943"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.02082-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.02082-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T13:03:28Z","timestamp":1744722208000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.02082-24"}},"subtitle":[],"editor":[{"given":"Martin","family":"Schwemmle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":53,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4,15]]}},"alternative-id":["10.1128\/jvi.02082-24"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02082-24","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]},"assertion":[{"value":"2024-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02082-24"}}