1. Microbiology and Infectious Disease
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pp32 and APRIL are host cell-derived regulators of influenza virus RNA synthesis from cRNA

  1. Kenji Sugiyama
  2. Atsushi Kawaguchi
  3. Mitsuru Okuwaki
  4. Kyosuke Nagata  Is a corresponding author
  1. University of Tsukuba, Japan
Research Article
  • Cited 41
  • Views 2,355
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Cite this article as: eLife 2015;4:e08939 doi: 10.7554/eLife.08939

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.

Article and author information

Author details

  1. Kenji Sugiyama

    Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Atsushi Kawaguchi

    Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Mitsuru Okuwaki

    Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Kyosuke Nagata

    Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
    For correspondence
    knagata@md.tsukuba.ac.jp
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: May 26, 2015
  2. Accepted: October 20, 2015
  3. Accepted Manuscript published: October 29, 2015 (version 1)
  4. Version of Record published: January 7, 2016 (version 2)
  5. Version of Record updated: February 21, 2017 (version 3)

Copyright

© 2015, Sugiyama et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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