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

Author:

Anderson Danielle E.1,Pfeffermann Kristin2,Kim So Young34,Sawatsky Bevan2ORCID,Pearson James34,Kovtun Mikhail3,Corcoran David L.3,Krebs Yvonne2,Sigmundsson Kristmundur5,Jamison Sharon F.3,Yeo Zhen Zhen Joanna1,Rennick Linda J.6,Wang Lin-Fa1ORCID,Talbot Pierre J.7,Duprex W. Paul6,Garcia-Blanco Mariano A.1348ORCID,von Messling Veronika127ORCID

Affiliation:

1. Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore

2. Veterinary Medicine Division, Paul-Ehrlich-Institute, Langen, Germany

3. Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, USA

4. Duke Center for RNA Biology, Duke University, Durham, North Carolina, USA

5. Programme in Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore, Singapore

6. National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, USA

7. INRS-Institut Armand-Frappier, University of Quebec, Laval, Canada

8. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA

Abstract

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.

Funder

Canadian Institutes of Health Research

Canada Foundation for Innovation

German Center for Infection Research

NMRC

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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