{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T20:41:56Z","timestamp":1781901716030,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:00:00Z","timestamp":1613088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI138052, AI139392"],"award-info":[{"award-number":["AI138052, AI139392"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY031465"],"award-info":[{"award-number":["EY031465"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Filoviruses Ebola (EBOV) and Marburg (MARV) are devastating high-priority pathogens capable of causing explosive outbreaks with high human mortality rates. The matrix proteins of EBOV and MARV, as well as eVP40 and mVP40, respectively, are the key viral proteins that drive virus assembly and egress and can bud independently from cells in the form of virus-like particles (VLPs). The matrix proteins utilize proline-rich Late (L) domain motifs (e.g., PPxY) to hijack specific host proteins that contain WW domains, such as the HECT family E3 ligases, to facilitate the last step of virus\u2013cell separation. We identified E3 ubiquitin ligase Smad Ubiquitin Regulatory Factor 2 (SMURF2) as a novel interactor with VP40 that positively regulates VP40 VLP release. Our results show that eVP40 and mVP40 interact with the three WW domains of SMURF2 via their PPxY motifs. We provide evidence that the eVP40\u2013SMURF2 interaction is functional as the expression of SMURF2 positively regulates VLP egress, while siRNA knockdown of endogenous SMURF2 decreases VLP budding compared to controls. In sum, our identification of novel interactor SMURF2 adds to the growing list of identified host proteins that can regulate PPxY-mediated egress of VP40 VLPs. A more comprehensive understanding of the modular interplay between filovirus VP40 and host proteins may lead to the development of new therapies to combat these deadly infections.<\/jats:p>","DOI":"10.3390\/v13020288","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T18:46:31Z","timestamp":1613155591000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ubiquitin Ligase SMURF2 Interacts with Filovirus VP40 and Promotes Egress of VP40 VLPs"],"prefix":"10.3390","volume":"13","author":[{"given":"Ariel","family":"Shepley-McTaggart","sequence":"first","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Patrick","family":"Schwoerer","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cari A.","family":"Sagum","sequence":"additional","affiliation":[{"name":"Department of Epigenetics &amp; Molecular Carcinogenesis, M.D. Anderson Cancer Center, University of Texas, Smithville, TX 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Bedford","sequence":"additional","affiliation":[{"name":"Department of Epigenetics &amp; Molecular Carcinogenesis, M.D. Anderson Cancer Center, University of Texas, Smithville, TX 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-1137","authenticated-orcid":false,"given":"Chaitanya K.","family":"Jaladanki","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, Matrix #07-01, Singapore 138671, Singapore"},{"name":"Synthetic Biology Translational Research Programme, School of Medicine, National University of Singapore, Singapore 119077, Singapore"},{"name":"Programme in Cancer &amp; Stem Cell Biology, DUKE-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0199-9752","authenticated-orcid":false,"given":"Hao","family":"Fan","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, Matrix #07-01, Singapore 138671, Singapore"},{"name":"Synthetic Biology Translational Research Programme, School of Medicine, National University of Singapore, Singapore 119077, Singapore"},{"name":"Programme in Cancer &amp; Stem Cell Biology, DUKE-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Cassel","sequence":"additional","affiliation":[{"name":"Molecular Screening Facility, The Wistar Institute, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald N.","family":"Harty","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,12]]},"reference":[{"key":"ref_1","unstructured":"(2020, December 12). 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