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

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Cite this article as: eLife 2015;4:e08939 doi: 10.7554/eLife.08939

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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.

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Author details

Kenji Sugiyama

Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Competing interests
The authors declare that no competing interests exist.
Atsushi Kawaguchi

Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Competing interests
The authors declare that no competing interests exist.
Mitsuru Okuwaki

Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan

Competing interests
The authors declare that no competing interests exist.
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

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

Publication history

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

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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.