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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nüesch, J. P. F.
Right arrow Articles by Rommelaere, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nüesch, J. P. F.
Right arrow Articles by Rommelaere, J.

 Previous Article  |  Next Article 

Journal of Virology, May 2006, p. 4729-4739, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4729-4739.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

NS1 Interaction with CKII{alpha}: Novel Protein Complex Mediating Parvovirus-Induced Cytotoxicity

Jürg P. F. Nüesch* and Jean Rommelaere

Program Infection and Cancer, Abteilung F010, and Institut National de la Santé et de la Recherche Médicale U701, Deutsches Krebsforschungszentrum, Heidelberg, Germany

Received 22 December 2005/ Accepted 28 February 2006

During a productive infection, the prototype strain of the parvovirus minute virus of mice (MVMp) induces dramatic morphological alterations in permissive A9 fibroblasts, culminating in cell lysis at the end of infection. These cytopathic effects (CPE) result from rearrangements and destruction of the cytoskeletal micro- and intermediate filaments, while other structures such as the nuclear lamina and particularly the microtubule network remain protected throughout the infection (J. P. F. Nüesch et al., Virology 331:159-174, 2005). In order to unravel the mechanism(s) by which parvoviruses trigger CPE, we searched for NS1 interaction partners by differential affinity chromatography, using distinct NS1 mutants debilitated specifically for this function. Thereby, we isolated an NS1 partner polypeptide, whose interaction with NS1 correlated with the competence of the viral product for CPE induction, and further identified it by tandem mass spectrometry and Western blotting analyses to consist of the catalytic subunit of casein kinase II, CKII{alpha}. This interaction of NS1 with CKII{alpha} suggested interference by the viral protein with intracellular signaling. Using permanent cell lines expressing dominant-negative CKII{alpha} mutants, we were able to show that this kinase activity was indeed specifically involved in parvoviral CPE and progeny particle release. Furthermore, the NS1/CKII{alpha} complex proved to be able to specifically phosphorylate viral capsids, indicating a mediator function of NS1 for CKII activity and specificity, at least in vitro. Altogether our data suggest that parvovirus-induced CPE is mediated by NS1 interference with intracellular CKII signaling.

* Corresponding author. Mailing address: Program Infection and Cancer, Abt. F010 and INSERM U701, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, D-69120 Heidelberg, Germany. Phone: (49) 6221 424969. Fax: (49) 6221 424962. E-mail: jpf.nuesch{at}dkfz-heidelberg.de.

Journal of Virology, May 2006, p. 4729-4739, Vol. 80, No. 10
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.10.4729-4739.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nuesch, J. P. F., Bar, S., Lachmann, S., Rommelaere, J. (2009). Ezrin-Radixin-Moesin Family Proteins Are Involved in Parvovirus Replication and Spreading. J. Virol. 83: 5854-5863 [Abstract] [Full Text]  
  • Nuesch, J. P. F., Rommelaere, J. (2007). A viral adaptor protein modulating casein kinase II activity induces cytopathic effects in permissive cells. Proc. Natl. Acad. Sci. USA 104: 12482-12487 [Abstract] [Full Text]  


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