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 Law, L. M. J.
Right arrow Articles by Hobman, T. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Law, L. M. J.
Right arrow Articles by Hobman, T. C.

 Previous Article  |  Next Article 

Journal of Virology, February 2003, p. 1764-1771, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1764-1771.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Phosphorylation of Rubella Virus Capsid Regulates Its RNA Binding Activity and Virus Replication

Lok Man J. Law,1 Jason C. Everitt,1 Martin D. Beatch,1 Charles F. B. Holmes,2,3 and Tom C. Hobman1,3*

Departments of Cell Biology,1 Biochemistry,2 Signal Transduction Research Group, University of Alberta, Edmonton, Alberta T6G 2H7, Canada3

Received 4 September 2002/ Accepted 24 October 2002

Rubella virus is an enveloped positive-strand RNA virus of the family Togaviridae. Virions are composed of three structural proteins: a capsid and two membrane-spanning glycoproteins, E2 and E1. During virus assembly, the capsid interacts with genomic RNA to form nucleocapsids. In the present study, we have investigated the role of capsid phosphorylation in virus replication. We have identified a single serine residue within the RNA binding region that is required for normal phosphorylation of this protein. The importance of capsid phosphorylation in virus replication was demonstrated by the fact that recombinant viruses encoding hypophosphorylated capsids replicated at much lower titers and were less cytopathic than wild-type virus. Nonphosphorylated mutant capsid proteins exhibited higher affinities for viral RNA than wild-type phosphorylated capsids. Capsid protein isolated from wild-type strain virions bound viral RNA more efficiently than cell-associated capsid. However, the RNA-binding activity of cell-associated capsids increased dramatically after treatment with phosphatase, suggesting that the capsid is dephosphorylated during virus assembly. In vitro assays indicate that the capsid may be a substrate for protein phosphatase 1A. As capsid is heavily phosphorylated under conditions where virus assembly does not occur, we propose that phosphorylation serves to negatively regulate binding of viral genomic RNA. This may delay the initiation of nucleocapsid assembly until sufficient amounts of virus glycoproteins accumulate at the budding site and/or prevent nonspecific binding to cellular RNA when levels of genomic RNA are low. It follows that at a late stage in replication, the capsid may undergo dephosphorylation before nucleocapsid assembly occurs.

* Corresponding author. Mailing address: Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, 5-14 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada. Phone: (780) 492-6485. Fax: (780) 492-0450. E-mail: tom.hobman{at}ualberta.ca.

Journal of Virology, February 2003, p. 1764-1771, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1764-1771.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wu, C.-H., Yeh, S.-H., Tsay, Y.-G., Shieh, Y.-H., Kao, C.-L., Chen, Y.-S., Wang, S.-H., Kuo, T.-J., Chen, D.-S., Chen, P.-J. (2009). Glycogen Synthase Kinase-3 Regulates the Phosphorylation of Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein and Viral Replication. J. Biol. Chem. 284: 5229-5239 [Abstract] [Full Text]  
  • Ilkow, C. S., Mancinelli, V., Beatch, M. D., Hobman, T. C. (2008). Rubella Virus Capsid Protein Interacts with Poly(A)-Binding Protein and Inhibits Translation. J. Virol. 82: 4284-4294 [Abstract] [Full Text]  
  • Law, L. J., Ilkow, C. S., Tzeng, W.-P., Rawluk, M., Stuart, D. T., Frey, T. K., Hobman, T. C. (2006). Analyses of Phosphorylation Events in the Rubella Virus Capsid Protein: Role in Early Replication Events. J. Virol. 80: 6917-6925 [Abstract] [Full Text]  
  • Tzeng, W.-P., Matthews, J. D., Frey, T. K. (2006). Analysis of rubella virus capsid protein-mediated enhancement of replicon replication and mutant rescue.. J. Virol. 80: 3966-3974 [Abstract] [Full Text]  
  • Beatch, M. D., Everitt, J. C., Law, L. J., Hobman, T. C. (2005). Interactions between Rubella Virus Capsid and Host Protein p32 Are Important for Virus Replication. J. Virol. 79: 10807-10820 [Abstract] [Full Text]  
  • Calvo, E., Escors, D., Lopez, J. A., Gonzalez, J. M., Alvarez, A., Arza, E., Enjuanes, L. (2005). Phosphorylation and subcellular localization of transmissible gastroenteritis virus nucleocapsid protein in infected cells. J. Gen. Virol. 86: 2255-2267 [Abstract] [Full Text]  
  • Modrof, J., Lymperopoulos, K., Roy, P. (2005). Phosphorylation of Bluetongue Virus Nonstructural Protein 2 Is Essential for Formation of Viral Inclusion Bodies. J. Virol. 79: 10023-10031 [Abstract] [Full Text]  
  • Chen, M.-H., Icenogle, J. P. (2004). Rubella Virus Capsid Protein Modulates Viral Genome Replication and Virus Infectivity. J. Virol. 78: 4314-4322 [Abstract] [Full Text]  
  • Tzeng, W.-P., Frey, T. K. (2003). Complementation of a Deletion in the Rubella Virus P150 Nonstructural Protein by the Viral Capsid Protein. J. Virol. 77: 9502-9510 [Abstract] [Full Text]  
  • Ivanov, K. I., Puustinen, P., Gabrenaite, R., Vihinen, H., Ronnstrand, L., Valmu, L., Kalkkinen, N., Makinen, K. (2003). Phosphorylation of the Potyvirus Capsid Protein by Protein Kinase CK2 and Its Relevance for Virus Infection. Plant Cell 15: 2124-2139 [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»