{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:57:23Z","timestamp":1792598243002,"version":"4.5.0"},"reference-count":36,"publisher":"Microbiology Society","issue":"12","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,8]]},"abstract":"<jats:p>The zoonotic rabies virus (RABV) is a non-segmented negative-sense RNA virus classified within the family <jats:italic>Rhabdoviridae<\/jats:italic>, and is the most common aetiological agent responsible for fatal rabies disease. The RABV glycoprotein (G) forms trimeric spikes that protrude from RABV virions and mediate virus attachment, entry and spread, and is a major determinant of RABV pathogenesis. A range of RABV strains exist that are highly pathogenic in part due to their ability to evade host immune detection. However, some strains are disease-attenuated and can be cleared by host defences. A detailed molecular understanding of how strain variation relates to pathogenesis is currently lacking. Here, we reveal key differences in the trafficking profiles of RABV-G proteins from the challenge virus standard strain (CVS-11) and a highly attenuated vaccine strain SAD-B19 (SAD). We show that CVS-G traffics to the cell surface and undergoes rapid internalization through both clathrin- and cholesterol-dependent endocytic pathways. In contrast, SAD-G remains resident at the plasma membrane and internalizes at a significantly slower rate. Through engineering hybrids of CVS-G and SAD-G, we show that the cytoplasmic tail of CVS-G is the key determinant of these different internalization profiles. Alanine scanning further revealed that mutation of Y497 in CVS-G (H497 in SAD-G) could reduce the rate of internalization to SAD-G levels. Together, these data reveal new phenotypic differences between CVS-G and SAD-G proteins that may contribute to altered <jats:italic>in vivo<\/jats:italic> pathogenicity.<\/jats:p>","DOI":"10.1099\/jgv.0.001935","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T12:17:06Z","timestamp":1702037826000},"source":"Crossref","is-referenced-by-count":4,"title":["Internalization of rabies virus glycoprotein differs between pathogenic and attenuated virus strains"],"prefix":"10.1099","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-4860","authenticated-orcid":false,"given":"Ibrahim","family":"Almasoud","sequence":"first","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"},{"name":"Present address: Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait City, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Charlton","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Finke","sequence":"additional","affiliation":[{"name":"Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9035-2039","authenticated-orcid":false,"given":"John N.","family":"Barr","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamel","family":"Mankouri","sequence":"additional","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","volume-title":"World Health Organization WHO Expert Consultation on Rabies: Third Report","year":"2018"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.2310\/7060.2005.12055"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000339"},{"key":"R4","first-page":"360","article-title":"Re-evaluating the burden of rabies in Africa and Asia","volume":"83","author":"Knobel","year":"2005","journal-title":"Bull World Health Organ"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2018.11"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-100114-055157"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2019.02.006"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.125.3.447"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1007\/BF01314774"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1080\/13550280500385310"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.3390\/cells9020412"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.3109\/13550280009018301"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407289101"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.3390\/v11030218"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02092-14"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.3390\/v13101989"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2005.04.004"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111949"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2020.108699"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.031484"},{"key":"R21","doi-asserted-by":"crossref","first-page":"10690","DOI":"10.1016\/S0021-9258(19)50073-4","article-title":"N-linked glycosylation of rabies virus glycoprotein. Individual sequons differ in their glycosylation efficiencies and influence on cell surface expression","volume":"267","author":"Shakin-Eshleman","year":"1992","journal-title":"J Biol Chem"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.047852-0"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.53.3.926-934.1985"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2007.03.003"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2012.01.002"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2013.10.015"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.1.249-260.2000"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.13.6845-6851.2002"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01853-09"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204844200"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(90)90433-r"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.004"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth999"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-010-0743-8"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-6-366"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000542"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.001935?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T12:17:10Z","timestamp":1702037830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/jgv.0.001935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,8]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12,8]]}},"URL":"https:\/\/doi.org\/10.1099\/jgv.0.001935","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,8]]}}}