A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition

The complement system is a critical host defense against infection, playing a protective role that can also enhance disease if dysregulated. Although many consequences of complement activation during viral infection are well established, mechanisms that determine the extent to which viruses activate...

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Autores principales:	Jessica P Kuppan, Margaret D Mitrovich, Michael D Vahey
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	respiratory syncytial virus complement fluorescence imaging antibodies Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/8015c2897c71468badb2fbf9579102ee
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spelling	oai:doaj.org-article:8015c2897c71468badb2fbf9579102ee2021-12-01T10:59:40ZA morphological transformation in respiratory syncytial virus leads to enhanced complement deposition10.7554/eLife.705752050-084Xe70575https://doaj.org/article/8015c2897c71468badb2fbf9579102ee2021-09-01T00:00:00Zhttps://elifesciences.org/articles/70575https://doaj.org/toc/2050-084XThe complement system is a critical host defense against infection, playing a protective role that can also enhance disease if dysregulated. 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.Jessica P KuppanMargaret D MitrovichMichael D VaheyeLife Sciences Publications Ltdarticlerespiratory syncytial viruscomplementfluorescence imagingantibodiesMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	respiratory syncytial virus complement fluorescence imaging antibodies Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	respiratory syncytial virus complement fluorescence imaging antibodies Medicine R Science Q Biology (General) QH301-705.5 Jessica P Kuppan Margaret D Mitrovich Michael D Vahey A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition
description	The complement system is a critical host defense against infection, playing a protective role that can also enhance disease if dysregulated. 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.
format	article
author	Jessica P Kuppan Margaret D Mitrovich Michael D Vahey
author_facet	Jessica P Kuppan Margaret D Mitrovich Michael D Vahey
author_sort	Jessica P Kuppan
title	A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition
title_short	A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition
title_full	A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition
title_fullStr	A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition
title_full_unstemmed	A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition
title_sort	morphological transformation in respiratory syncytial virus leads to enhanced complement deposition
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/8015c2897c71468badb2fbf9579102ee
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_version_	1718405241791053824

A morphological transformation in respiratory syncytial virus leads to enhanced complement deposition

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