title: Genome-wide analysis of host factors in nodavirus RNA replication.
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.
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Linhui
authors.initials: L
authors.lastname: Hao
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Brett
authors.initials: B
authors.lastname: Lindenbach
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Billy
authors.initials: B
authors.lastname: Dye
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Kushner
authors.affiliation: Department of Statistics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Statistics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Newton
authors.affiliation: Institute for Molecular Virology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, Wisconsin, United States of America; Morgridge Institute for Research, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
authors.forename: Paul
authors.initials: P
authors.lastname: Ahlquist
mesh_terms: D055106:Genome-Wide Association Study / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D012328:RNA Viruses / Q000235:genetics / Q000502:physiology; D012367:RNA, Viral / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics* / Q000502:physiology
chemical_list: D012367:RNA, Viral
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