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

Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE

Original Publication: Washington, D.C. : American Society for Microbiology

ATP-Binding Cassette Transporters/*genetics ; Host Microbial Interactions/*genetics ; Paramyxoviridae/*pathogenicity ; Pneumovirus/*pathogenicity; A549 Cells ; Computational Biology ; Gene Expression ; Humans ; RNA, Messenger ; RNA, Small Interfering ; RNA-Binding Proteins/genetics

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.
(Copyright © 2019 Anderson et al.)

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R01 AI089526 United States AI NIAID NIH HHS; R01 AI099100 United States AI NIAID NIH HHS; R01 AI101431 United States AI NIAID NIH HHS; MOP-66989 Canada CIHR

Keywords: ABCE1; Paramyxoviridae; Pneumoviridae; RNAi screen; host factor; respiratory syncytial virus

0 (ABCE1 protein, human)
0 (ATP-Binding Cassette Transporters)
0 (RNA, Messenger)
0 (RNA, Small Interfering)
0 (RNA-Binding Proteins)

Date Created: 20190516 Date Completed: 20190705 Latest Revision: 20200309

20221213

PMC6520455

10.1128/mBio.00826-19

31088929