pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA

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...

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Main Authors: Kenji Sugiyama, Atsushi Kawaguchi, Mitsuru Okuwaki, Kyosuke Nagata
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/08939
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author Kenji Sugiyama
Atsushi Kawaguchi
Mitsuru Okuwaki
Kyosuke Nagata
author_facet Kenji Sugiyama
Atsushi Kawaguchi
Mitsuru Okuwaki
Kyosuke Nagata
author_sort Kenji Sugiyama
collection DOAJ
description 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.
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spelling doaj.art-2587074cbb2a46cf9c387b222f9b11742022-12-22T03:52:46ZengeLife Sciences Publications LtdeLife2050-084X2015-10-01410.7554/eLife.08939pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNAKenji Sugiyama0Atsushi Kawaguchi1Mitsuru Okuwaki2Kyosuke Nagata3https://orcid.org/0000-0003-2522-3561Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanReplication 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.https://elifesciences.org/articles/08939ANP32de novohost factorinfluenzareplicationRNA dependent RNA polymerase
spellingShingle Kenji Sugiyama
Atsushi Kawaguchi
Mitsuru Okuwaki
Kyosuke Nagata
pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
eLife
ANP32
de novo
host factor
influenza
replication
RNA dependent RNA polymerase
title pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
title_full pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
title_fullStr pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
title_full_unstemmed pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
title_short pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA
title_sort pp32 and april are host cell derived regulators of influenza virus rna synthesis from crna
topic ANP32
de novo
host factor
influenza
replication
RNA dependent RNA polymerase
url https://elifesciences.org/articles/08939
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