Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>

ABSTRACT Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identif...

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Autores principales:	Danielle E. Anderson, Kristin Pfeffermann, So Young Kim, Bevan Sawatsky, James Pearson, Mikhail Kovtun, David L. Corcoran, Yvonne Krebs, Kristmundur Sigmundsson, Sharon F. Jamison, Zhen Zhen Joanna Yeo, Linda J. Rennick, Lin-Fa Wang, Pierre J. Talbot, W. Paul Duprex, Mariano A. Garcia-Blanco, Veronika von Messling
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	ABCE1 Paramyxoviridae Pneumoviridae RNAi screen host factor respiratory syncytial virus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/458b77fa67604a6a92aa29f115dcdb71
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spelling	oai:doaj.org-article:458b77fa67604a6a92aa29f115dcdb712021-11-15T15:55:25ZComparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>10.1128/mBio.00826-192150-7511https://doaj.org/article/458b77fa67604a6a92aa29f115dcdb712019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00826-19https://doaj.org/toc/2150-7511ABSTRACT Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and translation as the top pathways required by all three viruses. As the top hit in the translation pathway, ABCE1, a member of the ATP-binding cassette transporters, was chosen for further study. We found that ABCE1 supports replication of all three viruses, confirming its importance for viruses of both families. More detailed characterization revealed that ABCE1 is specifically required for efficient viral but not general cellular protein synthesis, indicating that paramyxoviral and pneumoviral mRNAs exploit specific translation mechanisms. In addition to providing a novel overview of cellular proteins and pathways that impact these important pathogens, this study highlights the role of ABCE1 as a host factor required for efficient paramyxovirus and pneumovirus translation. IMPORTANCE The Paramyxoviridae and Pneumoviridae families include important human and animal pathogens. To identify common host factors, we performed genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in the same cell line. A comparative bioinformatics analysis yielded different members of the coatomer complex I, translation factors ABCE1 and eIF3A, and several RNA binding proteins as cellular proteins with proviral activity for all three viruses. A more detailed characterization of ABCE1 revealed its essential role for viral protein synthesis. Taken together, these data sets provide new insight into the interactions between paramyxoviruses and pneumoviruses and host cell proteins and constitute a starting point for the development of broadly effective antivirals.Danielle E. AndersonKristin PfeffermannSo Young KimBevan SawatskyJames PearsonMikhail KovtunDavid L. CorcoranYvonne KrebsKristmundur SigmundssonSharon F. JamisonZhen Zhen Joanna YeoLinda J. RennickLin-Fa WangPierre J. TalbotW. Paul DuprexMariano A. Garcia-BlancoVeronika von MesslingAmerican Society for MicrobiologyarticleABCE1ParamyxoviridaePneumoviridaeRNAi screenhost factorrespiratory syncytial virusMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	ABCE1 Paramyxoviridae Pneumoviridae RNAi screen host factor respiratory syncytial virus Microbiology QR1-502
spellingShingle	ABCE1 Paramyxoviridae Pneumoviridae RNAi screen host factor respiratory syncytial virus Microbiology QR1-502 Danielle E. Anderson Kristin Pfeffermann So Young Kim Bevan Sawatsky James Pearson Mikhail Kovtun David L. Corcoran Yvonne Krebs Kristmundur Sigmundsson Sharon F. Jamison Zhen Zhen Joanna Yeo Linda J. Rennick Lin-Fa Wang Pierre J. Talbot W. Paul Duprex Mariano A. Garcia-Blanco Veronika von Messling Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>
description	ABSTRACT Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and translation as the top pathways required by all three viruses. As the top hit in the translation pathway, ABCE1, a member of the ATP-binding cassette transporters, was chosen for further study. We found that ABCE1 supports replication of all three viruses, confirming its importance for viruses of both families. More detailed characterization revealed that ABCE1 is specifically required for efficient viral but not general cellular protein synthesis, indicating that paramyxoviral and pneumoviral mRNAs exploit specific translation mechanisms. In addition to providing a novel overview of cellular proteins and pathways that impact these important pathogens, this study highlights the role of ABCE1 as a host factor required for efficient paramyxovirus and pneumovirus translation. IMPORTANCE The Paramyxoviridae and Pneumoviridae families include important human and animal pathogens. To identify common host factors, we performed genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in the same cell line. A comparative bioinformatics analysis yielded different members of the coatomer complex I, translation factors ABCE1 and eIF3A, and several RNA binding proteins as cellular proteins with proviral activity for all three viruses. A more detailed characterization of ABCE1 revealed its essential role for viral protein synthesis. Taken together, these data sets provide new insight into the interactions between paramyxoviruses and pneumoviruses and host cell proteins and constitute a starting point for the development of broadly effective antivirals.
format	article
author	Danielle E. Anderson Kristin Pfeffermann So Young Kim Bevan Sawatsky James Pearson Mikhail Kovtun David L. Corcoran Yvonne Krebs Kristmundur Sigmundsson Sharon F. Jamison Zhen Zhen Joanna Yeo Linda J. Rennick Lin-Fa Wang Pierre J. Talbot W. Paul Duprex Mariano A. Garcia-Blanco Veronika von Messling
author_facet	Danielle E. Anderson Kristin Pfeffermann So Young Kim Bevan Sawatsky James Pearson Mikhail Kovtun David L. Corcoran Yvonne Krebs Kristmundur Sigmundsson Sharon F. Jamison Zhen Zhen Joanna Yeo Linda J. Rennick Lin-Fa Wang Pierre J. Talbot W. Paul Duprex Mariano A. Garcia-Blanco Veronika von Messling
author_sort	Danielle E. Anderson
title	Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>
title_short	Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>
title_full	Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>
title_fullStr	Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>
title_full_unstemmed	Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>
title_sort	comparative loss-of-function screens reveal abce1 as an essential cellular host factor for efficient translation of <italic toggle="yes">paramyxoviridae</italic> and <italic toggle="yes">pneumoviridae</italic>
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/458b77fa67604a6a92aa29f115dcdb71
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Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of <italic toggle="yes">Paramyxoviridae</italic> and <italic toggle="yes">Pneumoviridae</italic>

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