{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:27:19Z","timestamp":1785824839984,"version":"3.56.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009729","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000}}],"reference-count":93,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1125704"],"award-info":[{"award-number":["1125704"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1079211"],"award-info":[{"award-number":["1079211"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1003244"],"award-info":[{"award-number":["1003244"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1160838"],"award-info":[{"award-number":["1160838"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1174405"],"award-info":[{"award-number":["1174405"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["DP150102569"],"award-info":[{"award-number":["DP150102569"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]},{"name":"meigunyah trust grimwade fellowship"},{"name":"Australian Government Research Training Program Scholarship"},{"name":"Melbourne Research Scholarship"},{"name":"Melbourne Research Scholarship"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Rabies virus phosphoprotein (P protein) is a multifunctional protein that plays key roles in replication as the polymerase cofactor that binds to the complex of viral genomic RNA and the nucleoprotein (N protein), and in evading the innate immune response by binding to STAT transcription factors. These interactions are mediated by the C-terminal domain of P (P<jats:sub>CTD<\/jats:sub>). The colocation of these binding sites in the small globular P<jats:sub>CTD<\/jats:sub> raises the question of how these interactions underlying replication and immune evasion, central to viral infection, are coordinated and, potentially, coregulated. While direct data on the binding interface of the P<jats:sub>CTD<\/jats:sub> for STAT1 is available, the lack of direct structural data on the sites that bind N protein limits our understanding of this interaction hub. The P<jats:sub>CTD<\/jats:sub> was proposed to bind <jats:italic>via<\/jats:italic> two sites to a flexible loop of N protein (N<jats:sub>pep<\/jats:sub>) that is not visible in crystal structures, but no direct analysis of this interaction has been reported. Here we use Nuclear Magnetic Resonance, and molecular modelling to show N protein residues, Leu381, Asp383, Asp384 and phosphor-Ser389, are likely to bind to a \u2018positive patch\u2019 of the P<jats:sub>CTD<\/jats:sub> formed by Lys211, Lys214 and Arg260. Furthermore, in contrast to previous predictions we identify a single site of interaction on the P<jats:sub>CTD<\/jats:sub> by this N<jats:sub>pep<\/jats:sub>. Intriguingly, this site is proximal to the defined STAT1 binding site that includes Ile201 to Phe209. However, cell-based assays indicate that STAT1 and N protein do not compete for P protein. Thus, it appears that interactions critical to replication and immune evasion can occur simultaneously with the same molecules of P protein so that the binding of P protein to activated STAT1 can potentially occur without interrupting interactions involved in replication. These data suggest that replication complexes might be directly involved in STAT1 antagonism.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009729","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T17:37:29Z","timestamp":1625765849000},"page":"e1009729","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":22,"title":["Definition of the immune evasion-replication interface of rabies virus P protein"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8940-3663","authenticated-orcid":true,"given":"Jingyu","family":"Zhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela R.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-4301","authenticated-orcid":true,"given":"Stephanie","family":"Portelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh Binh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isshu","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5566-5638","authenticated-orcid":true,"given":"Siqiong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2347-4079","authenticated-orcid":true,"given":"Tatsunori","family":"Masatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Rawlinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4220-3597","authenticated-orcid":true,"given":"Ashish","family":"Sethi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0296-966X","authenticated-orcid":true,"given":"Naoto","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-2413","authenticated-orcid":true,"given":"David B.","family":"Ascher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-3906","authenticated-orcid":true,"given":"Gregory W.","family":"Moseley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-449X","authenticated-orcid":true,"given":"Paul R.","family":"Gooley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"issue":"8","key":"ppat.1009729.ref001","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1007\/s00705-018-3814-x","article-title":"Taxonomy of the order Mononegavirales: update 2018","volume":"163","author":"GK Amarasinghe","year":"2018","journal-title":"Arch Virol"},{"issue":"7","key":"ppat.1009729.ref002","first-page":"77","article-title":"Human rabies: 2016 updates and call for data","volume":"92","year":"2017","journal-title":"Wkly Epidemiol Rec"},{"issue":"4","key":"ppat.1009729.ref003","doi-asserted-by":"crossref","first-page":"e0003709","DOI":"10.1371\/journal.pntd.0003709","article-title":"Estimating the global burden of endemic canine rabies","volume":"9","author":"K Hampson","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"982","key":"ppat.1009729.ref004","first-page":"1","article-title":"WHO Expert Consultation on Rabies. 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