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 A. Garcia-Blanco, Veronika von Messling

Research output: Contribution to journalArticle

4 Scopus citations

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 paramyxo-viral 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 pro-viral 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)
Article numbere00826-19
JournalmBio
Volume10
Issue number3
DOIs
StatePublished - May 1 2019

Keywords

  • ABCE1
  • Host factor
  • Paramyxoviridae
  • Pneumoviridae
  • RNAi screen
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Microbiology
  • Virology

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    Anderson, D. E., Pfeffermann, K., Kim, S. Y., Sawatsky, B., Pearson, J., Kovtun, M., Corcoran, D. L., Krebs, Y., Sigmundsson, K., Jamison, S. F., Yeo, Z. Z. J., Rennick, L. J., Wang, L. F., Talbot, P. J., Duprex, W. P., Garcia-Blanco, M. A., & 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, 10(3), [e00826-19]. https://doi.org/10.1128/mBio.00826-19