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Genome-wide analysis of host factors in nodavirus RNA replication

Hao, L and Lindenbach, B and Wang, X and Dye, B and Kushner, D and He, Q and Newton, M and Ahlquist, P (2014) Genome-wide analysis of host factors in nodavirus RNA replication. PLoS ONE.

Abstract

Flock House virus (FHV), the best studied of the animal nodaviruses, has been used as a model for positive-strand RNA virus research. As one approach to identify host genes that affect FHV RNA replication, we performed a genome-wide analysis using a yeast single gene deletion library and a modified, reporter gene-expressing FHV derivative. A total of 4,491 yeast deletion mutants were tested for their ability to support FHV replication. Candidates for host genes modulating FHV replication were selected based on the initial genome-wide reporter gene assay and validated in repeated Northern blot assays for their ability to support wild type FHV RNA1 replication. Overall, 65 deletion strains were confirmed to show significant changes in the replication of both FHV genomic RNA1 and sub-genomic RNA3 with a false discovery rate of 5%. Among them, eight genes support FHV replication, since their deletion significantly reduced viral RNA accumulation, while 57 genes limit FHV replication, since their deletion increased FHV RNA accumulation. Of the gene products implicated in affecting FHV replication, three are localized to mitochondria, where FHV RNA replication occurs, 16 normally reside in the nucleus and may have indirect roles in FHV replication, and the remaining 46 are in the cytoplasm, with functions enriched in translation, RNA processing and trafficking. 2014 Hao et al

Item Type: Article
Additional Information: NIBR author: He, Q institute: NIBR- address only contributor address: (Hao, Lindenbach, Wang, Dye, Kushner, Ahlquist) Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI, United States (Hao, Ahlquist) Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI, United States (He, Newton) Department of Statistics, University of Wisconsin-Madison, Madison, WI, United States (Newton) Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, United States (Ahlquist) Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI, United States (Lindenbach) Center for RNA Science and Medicine, Yale University, New Haven, CT, United States (Wang) Department of Plant Pathology, Physiology and Weed Science, Virginia Tech., Blacksburg, VA, United States (Dye) Motlow State Community College, Smyrna, TN, United States (Kushner) Department of Biology, Dickinson College, Carlisle, PA, United States (He) Novartis Institute of Biomedical Research, Cambridge, MA, United States
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22666

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