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Journal of Virology, March 1999, p. 2222-2231, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Modulation of Nuclear Localization of the Influenza Virus Nucleoprotein through Interaction with Actin Filaments

Paul Digard,1,* Debra Elton,1 Konrad Bishop,1 Elizabeth Medcalf,1 Alan Weeds,2 and Brian Pope2

Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP,1 and Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH,2 United Kingdom

Received 16 September 1998/Accepted 1 December 1998

The influenza virus genome is transcribed in the nuclei of infected cells but assembled into progeny virions in the cytoplasm. This is reflected in the cellular distribution of the virus nucleoprotein (NP), a protein which encapsidates genomic RNA to form ribonucleoprotein structures. At early times postinfection NP is found in the nucleus, but at later times it is found predominantly in the cytoplasm. NP contains several sequences proposed to act as nuclear localization signals (NLSs), and it is not clear how these are overridden to allow cytoplasmic accumulation of the protein. We find that NP binds tightly to filamentous actin in vitro and have identified a cluster of residues in NP essential for the interaction. Complexes containing RNA, NP, and actin could be formed, suggesting that viral ribonucleoproteins also bind actin. In cells, exogenously expressed NP when expressed at a high level partitioned to the cytoplasm, where it associated with F-actin stress fibers. In contrast, mutants unable to bind F-actin efficiently were imported into the nucleus even under conditions of high-level expression. Similarly, nuclear import of NLS-deficient NP molecules was restored by concomitant disruption of F-actin binding. We propose that the interaction of NP with F-actin causes the cytoplasmic retention of influenza virus ribonucleoproteins.

* Corresponding author. Mailing address: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, United Kingdom. Phone: 44 1223 336921. Fax: 44 1223 336926. E-mail: pd1{at}mole.bio.cam.ac.uk.

Journal of Virology, March 1999, p. 2222-2231, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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