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Elife. 2015 Oct 29;4. pii: e08939. doi: 10.7554/eLife.08939.

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

Author information

1
Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

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.

KEYWORDS:

ANP32; RNA dependent RNA polymerase; de novo; host factor; human; infectious disease; influenza; microbiology; replication

PMID:
26512887
PMCID:
PMC4718810
DOI:
10.7554/eLife.08939
[Indexed for MEDLINE]
Free PMC Article

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