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>
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
Affiliations
Danielle E. Anderson
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
Kristin Pfeffermann
Veterinary Medicine Division, Paul-Ehrlich-Institute, Langen, Germany
So Young Kim
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA
Bevan Sawatsky
Veterinary Medicine Division, Paul-Ehrlich-Institute, Langen, Germany
James Pearson
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA
Mikhail Kovtun
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA
David L. Corcoran
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA
Yvonne Krebs
Veterinary Medicine Division, Paul-Ehrlich-Institute, Langen, Germany
Kristmundur Sigmundsson
Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore
Sharon F. Jamison
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA
Zhen Zhen Joanna Yeo
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
Linda J. Rennick
National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA
Lin-Fa Wang
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
Pierre J. Talbot
INRS-Institut Armand-Frappier, University of Quebec, Laval, Canada
W. Paul Duprex
National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA
Mariano A. Garcia-Blanco
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
Veronika von Messling
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore
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.