Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses

The live attenuated yellow fever virus (YFV) vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation...

Full description

Bibliographic Details
Main Authors:	Fernandez-Garcia, Maria Dolores, Meertens, Laurent, Chazal, Maxime, Hafirassou, Mohamed Lamine, Dejarnac, Ophélie, Zamborlini, Alessia, Despres, Philippe, Sauvonnet, Nathalie, Arenzana-Seisdedos, Fernando, Jouvenet, Nolwenn, Amara, Ali
Format:	Online
Language:	English
Published:	American Society of Microbiology 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752603/

id	pubmed-4752603
recordtype	oai_dc
spelling	pubmed-47526032016-02-13 Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses Fernandez-Garcia, Maria Dolores Meertens, Laurent Chazal, Maxime Hafirassou, Mohamed Lamine Dejarnac, Ophélie Zamborlini, Alessia Despres, Philippe Sauvonnet, Nathalie Arenzana-Seisdedos, Fernando Jouvenet, Nolwenn Amara, Ali Research Article The live attenuated yellow fever virus (YFV) vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation. American Society of Microbiology 2016-02-09 /pmc/articles/PMC4752603/ /pubmed/26861019 http://dx.doi.org/10.1128/mBio.01956-15 Text en Copyright © 2016 Fernandez-Garcia et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Fernandez-Garcia, Maria Dolores Meertens, Laurent Chazal, Maxime Hafirassou, Mohamed Lamine Dejarnac, Ophélie Zamborlini, Alessia Despres, Philippe Sauvonnet, Nathalie Arenzana-Seisdedos, Fernando Jouvenet, Nolwenn Amara, Ali
spellingShingle	Fernandez-Garcia, Maria Dolores Meertens, Laurent Chazal, Maxime Hafirassou, Mohamed Lamine Dejarnac, Ophélie Zamborlini, Alessia Despres, Philippe Sauvonnet, Nathalie Arenzana-Seisdedos, Fernando Jouvenet, Nolwenn Amara, Ali Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses
author_facet	Fernandez-Garcia, Maria Dolores Meertens, Laurent Chazal, Maxime Hafirassou, Mohamed Lamine Dejarnac, Ophélie Zamborlini, Alessia Despres, Philippe Sauvonnet, Nathalie Arenzana-Seisdedos, Fernando Jouvenet, Nolwenn Amara, Ali
author_sort	Fernandez-Garcia, Maria Dolores
title	Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses
title_short	Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses
title_full	Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses
title_fullStr	Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses
title_full_unstemmed	Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses
title_sort	vaccine and wild-type strains of yellow fever virus engage distinct entry mechanisms and differentially stimulate antiviral immune responses
description	The live attenuated yellow fever virus (YFV) vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation.
publisher	American Society of Microbiology
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752603/
_version_	1613538193174429696

Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses

Similar Items