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High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells

Zika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and is therefore considered one of the major determinants in ZIKV pathogenesis. Here we report a gene-wide mapping of...

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Detalles Bibliográficos
Autores principales: Gong, Danyang, Zhang, Tian-Hao, Zhao, Dawei, Du, Yushen, Chapa, Travis J., Shi, Yuan, Wang, Laurie, Contreras, Deisy, Zeng, Gang, Shi, Pei-Yong, Wu, Ting-Ting, Arumugaswami, Vaithilingaraja, Sun, Ren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135943/
https://www.ncbi.nlm.nih.gov/pubmed/30227960
http://dx.doi.org/10.1016/j.isci.2018.02.005
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author Gong, Danyang
Zhang, Tian-Hao
Zhao, Dawei
Du, Yushen
Chapa, Travis J.
Shi, Yuan
Wang, Laurie
Contreras, Deisy
Zeng, Gang
Shi, Pei-Yong
Wu, Ting-Ting
Arumugaswami, Vaithilingaraja
Sun, Ren
author_facet Gong, Danyang
Zhang, Tian-Hao
Zhao, Dawei
Du, Yushen
Chapa, Travis J.
Shi, Yuan
Wang, Laurie
Contreras, Deisy
Zeng, Gang
Shi, Pei-Yong
Wu, Ting-Ting
Arumugaswami, Vaithilingaraja
Sun, Ren
author_sort Gong, Danyang
collection PubMed
description Zika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and is therefore considered one of the major determinants in ZIKV pathogenesis. Here we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library, with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting glycosylation display the most divergence. By characterizing individual mutants, we show that ablation of glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, whereas it either has little impact on ZIKV infection on certain human cells or leads to decreased infection through the entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.
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spelling pubmed-61359432018-09-17 High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells Gong, Danyang Zhang, Tian-Hao Zhao, Dawei Du, Yushen Chapa, Travis J. Shi, Yuan Wang, Laurie Contreras, Deisy Zeng, Gang Shi, Pei-Yong Wu, Ting-Ting Arumugaswami, Vaithilingaraja Sun, Ren iScience Article Zika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and is therefore considered one of the major determinants in ZIKV pathogenesis. Here we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library, with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting glycosylation display the most divergence. By characterizing individual mutants, we show that ablation of glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, whereas it either has little impact on ZIKV infection on certain human cells or leads to decreased infection through the entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells. Elsevier 2018-03-23 /pmc/articles/PMC6135943/ /pubmed/30227960 http://dx.doi.org/10.1016/j.isci.2018.02.005 Text en © 2018 Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Gong, Danyang
Zhang, Tian-Hao
Zhao, Dawei
Du, Yushen
Chapa, Travis J.
Shi, Yuan
Wang, Laurie
Contreras, Deisy
Zeng, Gang
Shi, Pei-Yong
Wu, Ting-Ting
Arumugaswami, Vaithilingaraja
Sun, Ren
High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells
title High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells
title_full High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells
title_fullStr High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells
title_full_unstemmed High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells
title_short High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells
title_sort high-throughput fitness profiling of zika virus e protein reveals different roles for glycosylation during infection of mammalian and mosquito cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135943/
https://www.ncbi.nlm.nih.gov/pubmed/30227960
http://dx.doi.org/10.1016/j.isci.2018.02.005
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