Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae

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 Garcia-Blanco, Veronika von Messling

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalmBio
Volume10
Issue number3
DOIs
StatePublished - May 14 2019

Fingerprint

Paramyxoviridae
Pneumovirus
Viruses
Mumps
Respiratory Syncytial Viruses
Measles
Small Interfering RNA
Proteins
RNA Transport
Genome
Cell Line
ATP-Binding Cassette Transporters
RNA-Binding Proteins
Viral Proteins
Life Cycle Stages
Computational Biology
Respiratory System
Antiviral Agents
Messenger RNA

Keywords

  • ABCE1
  • host factor
  • Paramyxoviridae
  • Pneumoviridae
  • respiratory syncytial virus
  • RNAi screen

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae. / Anderson, Danielle E.; Pfeffermann, Kristin; Kim, So Young; Sawatsky, Bevan; Pearson, James; Kovtun, Mikhail; Corcoran, David L.; Krebs, Yvonne; Sigmundsson, Kristmundur; Jamison, Sharon F.; Yeo, Zhen Zhen Joanna; Rennick, Linda J.; Wang, Lin Fa; Talbot, Pierre J.; Duprex, W. Paul; Garcia-Blanco, Mariano; von Messling, Veronika.

In: mBio, Vol. 10, No. 3, 14.05.2019.

Research output: Contribution to journalArticle

Anderson, DE, Pfeffermann, K, Kim, SY, Sawatsky, B, Pearson, J, Kovtun, M, Corcoran, DL, Krebs, Y, Sigmundsson, K, Jamison, SF, Yeo, ZZJ, Rennick, LJ, Wang, LF, Talbot, PJ, Duprex, WP, Garcia-Blanco, M & von Messling, V 2019, 'Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae', mBio, vol. 10, no. 3. https://doi.org/10.1128/mBio.00826-19
Anderson, Danielle E. ; Pfeffermann, Kristin ; Kim, So Young ; Sawatsky, Bevan ; Pearson, James ; Kovtun, Mikhail ; Corcoran, David L. ; Krebs, Yvonne ; Sigmundsson, Kristmundur ; Jamison, Sharon F. ; Yeo, Zhen Zhen Joanna ; Rennick, Linda J. ; Wang, Lin Fa ; Talbot, Pierre J. ; Duprex, W. Paul ; Garcia-Blanco, Mariano ; von Messling, Veronika. / Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae. In: mBio. 2019 ; Vol. 10, No. 3.
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