Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae
| Autor: | Kristmundur Sigmundsson, Danielle E. Anderson, So Young Kim, Zhen Zhen Joanna Yeo, Sharon F. Jamison, Kristin Pfeffermann, James L. Pearson, Bevan Sawatsky, Mikhail Kovtun, Lin-Fa Wang, Pierre J. Talbot, Veronika von Messling, Mariano A. Garcia-Blanco, Yvonne Krebs, David L. Corcoran, Linda J. Rennick, W. Paul Duprex |
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| Přispěvatelé: | Duke-NUS Medical School [Singapore], Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines (EPI), Duke University [Durham], National Emerging Infectious Diseases Laboratories (NEIDL), Boston University [Boston] (BU), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), The University of Texas Medical Branch (UTMB), This work was supported by grants CIHR MOP-66989 of the Canadian Institutes of Health Research, CFI 9488 Canada Foundation for Innovation, DZIF TTU Emerging Infections SFB1021 of the German Center for Infection Research, and intramural funding of the German Ministry of Health to V.V.M., NMRC/BNIG/2030/2015 (Singapore) to D.E.A., and USA NIH R01-AI089526 and R01-AI101431 to M.A.G.-B. and R01-AI099100 to W.P.D., We thank members of our laboratories, past and present, for constructive comments throughout this project. We thank the Duke Functional Genomics Shared Resource for work related to the primary siRNA screens. We are grateful to Jaisri Lingappa for sharing the ABCE1 antibody and peptide sequence during our preliminary studies. We thank Ian Mendenhall for his assistance in the construction of the phylogenetic tree and Kevin Wittwer and Oliver Siering for technical assistance. We greatly appreciate the help provided by Robert Tampé, Ralph Wieneke, and Simon Trowitzsch with the phosphorimager and Andrea Maisner and Marc Ringel with the confocal microscope. We thank Stephan Becker for critical comments on the manuscript. |
| Rok vydání: | 2019 |
| Předmět: |
MESH: Gene Expression
Paramyxoviridae ABCE1 respiratory syncytial virus [SDV]Life Sciences [q-bio] host factor MESH: Pneumovirus/pathogenicity RNA-binding protein Computational biology Microbiology 03 medical and health sciences Virology MESH: RNA Small Interfering MESH: RNA-Binding Proteins/genetics MESH: ATP-Binding Cassette Transporters/genetics [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Pneumoviridae RNAi screen MESH: RNA Messenger 030304 developmental biology Host factor 0303 health sciences MESH: Humans biology MESH: Paramyxoviridae/pathogenicity 030302 biochemistry & molecular biology Translation (biology) Pneumovirus biology.organism_classification QR1-502 MESH: Host Microbial Interactions/genetics 3. Good health Vesicular transport protein biology.protein MESH: A549 Cells MESH: Computational Biology |
| Zdroj: | mBio mBio, American Society for Microbiology, 2019, 10 (3), pp.e00826-19. ⟨10.1128/mBio.00826-19⟩ mBio, Vol 10, Iss 3, p e00826-19 (2019) mBio, Vol 10, Iss 3 (2019) |
| ISSN: | 2150-7511 2161-2129 |
| DOI: | 10.1128/mbio.00826-19 |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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