Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies

ABSTRACT Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infec...

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Autores principales:	Emily N. Gallichotte, Ellen F. Young, Thomas J. Baric, Boyd L. Yount, Stefan W. Metz, Matthew C. Begley, Aravinda M. de Silva, Ralph S. Baric
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Zika virus chimeric virus epitope neutralizing antibodies Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f659dd33a20641e28415e64c39b45e5e
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spelling	oai:doaj.org-article:f659dd33a20641e28415e64c39b45e5e2021-11-15T15:59:42ZRole of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies10.1128/mBio.01485-192150-7511https://doaj.org/article/f659dd33a20641e28415e64c39b45e5e2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01485-19https://doaj.org/toc/2150-7511ABSTRACT Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIII-targeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines. IMPORTANCE Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIII-specific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines.Emily N. GallichotteEllen F. YoungThomas J. BaricBoyd L. YountStefan W. MetzMatthew C. BegleyAravinda M. de SilvaRalph S. BaricAmerican Society for MicrobiologyarticleZika viruschimeric virusepitopeneutralizing antibodiesMicrobiologyQR1-502ENmBio, Vol 10, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Zika virus chimeric virus epitope neutralizing antibodies Microbiology QR1-502
spellingShingle	Zika virus chimeric virus epitope neutralizing antibodies Microbiology QR1-502 Emily N. Gallichotte Ellen F. Young Thomas J. Baric Boyd L. Yount Stefan W. Metz Matthew C. Begley Aravinda M. de Silva Ralph S. Baric Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies
description	ABSTRACT Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIII-targeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines. IMPORTANCE Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIII-specific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines.
format	article
author	Emily N. Gallichotte Ellen F. Young Thomas J. Baric Boyd L. Yount Stefan W. Metz Matthew C. Begley Aravinda M. de Silva Ralph S. Baric
author_facet	Emily N. Gallichotte Ellen F. Young Thomas J. Baric Boyd L. Yount Stefan W. Metz Matthew C. Begley Aravinda M. de Silva Ralph S. Baric
author_sort	Emily N. Gallichotte
title	Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies
title_short	Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies
title_full	Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies
title_fullStr	Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies
title_full_unstemmed	Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies
title_sort	role of zika virus envelope protein domain iii as a target of human neutralizing antibodies
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/f659dd33a20641e28415e64c39b45e5e
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Role of Zika Virus Envelope Protein Domain III as a Target of Human Neutralizing Antibodies

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