title: pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA.
abstract: Replication of influenza viral genomic RNA (vRNA) is catalyzed by viral RNA-dependent RNA polymerase (vRdRP). Complementary RNA (cRNA) is first copied from vRNA, and progeny vRNAs are then amplified from the cRNA. Although vRdRP and viral RNA are minimal requirements, efficient cell-free replication could not be reproduced using only these viral factors. Using a biochemical complementation assay system, we found a novel activity in the nuclear extracts of uninfected cells, designated IREF-2, that allows robust unprimed vRNA synthesis from a cRNA template. IREF-2 was shown to consist of host-derived proteins, pp32 and APRIL. IREF-2 interacts with a free form of vRdRP and preferentially upregulates vRNA synthesis rather than cRNA synthesis. Knockdown experiments indicated that IREF-2 is involved in in vivo viral replication. On the basis of these results and those of previous studies, a plausible role(s) for IREF-2 during the initiation processes of vRNA replication is discussed.
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okuwaki
authors.affiliation: Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kyosuke
authors.identifier: http://orcid.org/0000-0003-2522-3561
authors.initials: K
authors.lastname: Nagata
mesh_terms: D002460:Cell Line; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D009975:Orthomyxoviridae / Q000502:physiology*; D025941:Protein Interaction Mapping; D018075:RNA, Complementary / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C087425:ANP32A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D018075:RNA, Complementary; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D012324:RNA-Dependent RNA Polymerase
keywords: ANP32; RNA dependent RNA polymerase; de novo; host factor; human; infectious disease; influenza; microbiology; replication