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Although many consequences of complement activation during viral infection are well established, mechanisms that determine the extent to which viruses activate complement remain elusive. Here, we investigate complement activation by human respiratory syncytial virus (RSV), a filamentous respiratory pathogen that causes significant morbidity and mortality. By engineering a strain of RSV harboring tags on the surface glycoproteins F and G, we are able to monitor opsonization of single RSV particles using fluorescence microscopy. These experiments reveal an antigenic hierarchy, where antibodies that bind toward the apex of F in either the pre- or postfusion conformation activate the classical pathway whereas other antibodies do not. Additionally, we identify an important role for virus morphology in complement activation: as viral filaments age, they undergo a morphological transformation which lowers the threshold for complement deposition through changes in surface curvature. Collectively, these results identify antigenic and biophysical characteristics of virus particles that contribute to the formation of viral immune complexes, and suggest models for how these factors may shape disease severity and adaptive immune responses to RSV.<\/jats:p>","DOI":"10.7554\/elife.70575","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T10:01:21Z","timestamp":1632909681000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.70575","source":"Crossref","is-referenced-by-count":12,"title":["A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-1876","authenticated-orcid":true,"given":"Jessica P","family":"Kuppan","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Center for Science & Engineering of Living Systems (CSELS), Washington University in St. Louis","place":["St. Louis, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1302-2837","authenticated-orcid":true,"given":"Margaret D","family":"Mitrovich","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Center for Science & Engineering of Living Systems (CSELS), Washington University in St. Louis","place":["St. Louis, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9453-4860","authenticated-orcid":true,"given":"Michael D","family":"Vahey","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Center for Science & Engineering of Living Systems (CSELS), Washington University in St. Louis","place":["St. Louis, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4374","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1128\/CVI.00609-15","article-title":"Brief history and characterization of enhanced respiratory syncytial virus disease","volume":"23","author":"Acosta","year":"2015","journal-title":"Clinical and Vaccine Immunology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"13996","DOI":"10.1073\/pnas.1210275109","article-title":"Structure and assembly of a Paramyxovirus matrix protein","volume":"109","author":"Battisti","year":"2012","journal-title":"PNAS"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/s41579-019-0149-x","article-title":"Respiratory syncytial virus entry and how to block it","volume":"17","author":"Battles","year":"2019","journal-title":"Nature Reviews. 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