Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions

Abstract HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a correct trimeric conformation, Env mediates virus–cell binding and fusion. Malfunctioning of this machinery renders virions incapable of infecting cells. Each HIV-1 virion carries 10–14 Envs, and therefore a defectiv...

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Autores principales:	Anush Arakelyan, Wendy Fitzgerald, Deborah F. King, Paul Rogers, Hannah M. Cheeseman, Jean-Charles Grivel, Robin J. Shattock, Leonid Margolis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b509b5f8ece4c71a2edbadc8ddbedb5
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spelling	oai:doaj.org-article:6b509b5f8ece4c71a2edbadc8ddbedb52021-12-02T15:05:25ZFlow virometry analysis of envelope glycoprotein conformations on individual HIV virions10.1038/s41598-017-00935-w2045-2322https://doaj.org/article/6b509b5f8ece4c71a2edbadc8ddbedb52017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00935-whttps://doaj.org/toc/2045-2322Abstract HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a correct trimeric conformation, Env mediates virus–cell binding and fusion. Malfunctioning of this machinery renders virions incapable of infecting cells. Each HIV-1 virion carries 10–14 Envs, and therefore a defective Env may not necessarily render a HIV virion non-infectious, since other Env on the same virion may still be functional. Alternatively, it is possible that on a given virion either all the spikes are defective or all are functional. Here, we investigate Env conformations on individual virions using our new nanotechnology, “flow virometry”, and a panel of antibodies that discriminate between various Env conformations. We found that the majority of HIV-1 virions carry either only trimeric (“functional”) or only defective spikes. The relatively small subfraction of virions that carry both functional and nonfunctional Envs contributes little to HIV infection of human lymphoid tissue ex vivo. The observation that the majority of virions exclusively express either functional or nonfunctional forms of Env has important implications for understanding the role of neutralizing and non-neutralizing antibodies in the immune control of HIV infection as well as for the development of effective prophylactic strategies.Anush ArakelyanWendy FitzgeraldDeborah F. KingPaul RogersHannah M. CheesemanJean-Charles GrivelRobin J. ShattockLeonid MargolisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anush Arakelyan Wendy Fitzgerald Deborah F. King Paul Rogers Hannah M. Cheeseman Jean-Charles Grivel Robin J. Shattock Leonid Margolis Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions
description	Abstract HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a correct trimeric conformation, Env mediates virus–cell binding and fusion. Malfunctioning of this machinery renders virions incapable of infecting cells. Each HIV-1 virion carries 10–14 Envs, and therefore a defective Env may not necessarily render a HIV virion non-infectious, since other Env on the same virion may still be functional. Alternatively, it is possible that on a given virion either all the spikes are defective or all are functional. Here, we investigate Env conformations on individual virions using our new nanotechnology, “flow virometry”, and a panel of antibodies that discriminate between various Env conformations. We found that the majority of HIV-1 virions carry either only trimeric (“functional”) or only defective spikes. The relatively small subfraction of virions that carry both functional and nonfunctional Envs contributes little to HIV infection of human lymphoid tissue ex vivo. The observation that the majority of virions exclusively express either functional or nonfunctional forms of Env has important implications for understanding the role of neutralizing and non-neutralizing antibodies in the immune control of HIV infection as well as for the development of effective prophylactic strategies.
format	article
author	Anush Arakelyan Wendy Fitzgerald Deborah F. King Paul Rogers Hannah M. Cheeseman Jean-Charles Grivel Robin J. Shattock Leonid Margolis
author_facet	Anush Arakelyan Wendy Fitzgerald Deborah F. King Paul Rogers Hannah M. Cheeseman Jean-Charles Grivel Robin J. Shattock Leonid Margolis
author_sort	Anush Arakelyan
title	Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions
title_short	Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions
title_full	Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions
title_fullStr	Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions
title_full_unstemmed	Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions
title_sort	flow virometry analysis of envelope glycoprotein conformations on individual hiv virions
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6b509b5f8ece4c71a2edbadc8ddbedb5
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Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions

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