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

Publication ,  Journal Article
Anderson, DE; Pfeffermann, K; Kim, SY; Sawatsky, B; Pearson, J; Kovtun, M; Corcoran, DL; Krebs, Y; Sigmundsson, K; Jamison, SF; Yeo, ZZJ ...
Published in: mBio
May 14, 2019

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.

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Published In

mBio

DOI

EISSN

2150-7511

Publication Date

May 14, 2019

Volume

10

Issue

3

Location

United States

Related Subject Headings

  • RNA-Binding Proteins
  • RNA, Small Interfering
  • RNA, Messenger
  • Pneumovirus
  • Paramyxoviridae
  • Humans
  • Host Microbial Interactions
  • Gene Expression
  • Computational Biology
  • ATP-Binding Cassette Transporters
 

Citation

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Anderson, D. E., Pfeffermann, K., Kim, S. Y., Sawatsky, B., Pearson, J., Kovtun, 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, 10(3). https://doi.org/10.1128/mBio.00826-19
Anderson, Danielle E., Kristin Pfeffermann, So Young Kim, Bevan Sawatsky, James Pearson, Mikhail Kovtun, David L. Corcoran, et al. “Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae.MBio 10, no. 3 (May 14, 2019). https://doi.org/10.1128/mBio.00826-19.
Anderson DE, Pfeffermann K, Kim SY, Sawatsky B, Pearson J, Kovtun M, et al. Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae. mBio. 2019 May 14;10(3).
Anderson, Danielle E., et al. “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, May 2019. Pubmed, doi:10.1128/mBio.00826-19.
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 L-F, Talbot PJ, Duprex WP, Garcia-Blanco MA, von Messling V. Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae. mBio. 2019 May 14;10(3).

Published In

mBio

DOI

EISSN

2150-7511

Publication Date

May 14, 2019

Volume

10

Issue

3

Location

United States

Related Subject Headings

  • RNA-Binding Proteins
  • RNA, Small Interfering
  • RNA, Messenger
  • Pneumovirus
  • Paramyxoviridae
  • Humans
  • Host Microbial Interactions
  • Gene Expression
  • Computational Biology
  • ATP-Binding Cassette Transporters