This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Ciancanelli, M. J.
Right arrow Articles by Basler, C. F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ciancanelli, M. J.
Right arrow Articles by Basler, C. F.

 Previous Article  |  Next Article 

Journal of Virology, August 2009, p. 7828-7841, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.02610-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nipah Virus Sequesters Inactive STAT1 in the Nucleus via a P Gene-Encoded Mechanism {triangledown}

Michael J. Ciancanelli,1 Valentina A. Volchkova,2,3,4,5 Megan L. Shaw,1 Viktor E. Volchkov,2,3,4,5* and Christopher F. Basler1*

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029,1 Laboratoire des Filovirus, INSERM U758, 21 av. Tony Garnier, Lyon F-69007, France,2 Université de Lyon, Lyon F-69007, France,3 Université Lyon 1, Villeurbanne F-69622, France,4 IFR 128 BioSciences Gerland-Lyon Sud, Lyon F-69007, France5

Received 17 December 2008/ Accepted 12 May 2009

The Nipah virus (NiV) phosphoprotein (P) gene encodes the C, P, V, and W proteins. P, V, and W, have in common an amino-terminal domain sufficient to bind STAT1, inhibiting its interferon (IFN)-induced tyrosine phosphorylation. P is also essential for RNA-dependent RNA polymerase function. C is encoded by an alternate open reading frame (ORF) within the common amino-terminal domain. Mutations within residues 81 to 113 of P impaired its polymerase cofactor function, as assessed by a minireplicon assay, but these mutants retained STAT1 inhibitory function. Mutations within the residue 114 to 140 region were identified that abrogated interaction with and inhibition of STAT1 by P, V, and W without disrupting P polymerase cofactor function. Recombinant NiVs were then generated. A G121E mutation, which abrogated inhibition of STAT1, was introduced into a C protein knockout background (Cko) because the mutation would otherwise also alter the overlapping C ORF. In cell culture, relative to the wild-type virus, the Cko mutation proved attenuating but the G121E mutant virus replicated identically to the Cko virus. In cells infected with the wild-type and Cko viruses, STAT1 was nuclear despite the absence of tyrosine phosphorylation. This latter observation mirrors what has been seen in cells expressing NiV W. In the G121E mutant virus-infected cells, STAT1 was not phosphorylated and was cytoplasmic in the absence of IFN stimulation but became tyrosine phosphorylated and nuclear following IFN addition. These data demonstrate that the gene for NiV P encodes functions that sequester inactive STAT1 in the nucleus, preventing its activation and suggest that the W protein is the dominant inhibitor of STAT1 in NiV-infected cells.

* Corresponding author. Mailing address for Christopher F. Basler: Department of Microbiology, P.O. Box 1124, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029. Phone: (212) 241-4847. Fax: (212) 534-1684. E-mail: chris.basler{at}mssm.edu. Mailing address for Viktor E. Volchkov: Filovirus Laboratory, INSERM U758, University Claude Bernard Lyon-1, 21 av. Tony Garnier, 69365 Lyon Cedex 07, France. Phone: 33 437282450. Fax: 33 437282459. E-mail: viktor.volchkov{at}inserm.fr

{triangledown} Published ahead of print on 10 June 2009.

Journal of Virology, August 2009, p. 7828-7841, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.02610-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»