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Journal of Virology, February 2004, p. 1992-2005, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1992-2005.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Members of a Novel Family of Mammalian Protein Kinases Complement the DNA-Negative Phenotype of a Vaccinia Virus ts Mutant Defective in the B1 Kinase

Kathleen A. Boyle and Paula Traktman*

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Received 18 September 2003/ Accepted 24 October 2003

Temperature-sensitive (ts) mutants of vaccinia virus defective in the B1 kinase demonstrate a conditionally lethal defect in DNA synthesis. B1 is the prototypic member of a new family of protein kinases (vaccinia virus-related kinases, or VRK) that possess distinctive B1-like sequence features within their catalytic motifs (R. J. Nichols and P. Traktman, J. Biol. Chem., in press). Given the striking sequence similarity between B1 and the VRK enzymes, we proposed that they might share overlapping substrate specificity. We therefore sought to determine whether the human and mouse VRK1 enzymes (hVRK1 and mVRK1, respectively) could complement a B1 deficiency in vivo. Recombinant ts2 viruses expressing hVRK1, mVRK1, or wild-type B1 were able to synthesize viral DNA at high temperature, but those expressing the more distantly related human casein kinase 1{alpha}2 could not. Complementation required the enzymatic activity of hVRK1, since a catalytically inactive allele of hVRK1 was unable to confer a temperature-insensitive phenotype. Interestingly, rescue of viral DNA synthesis was not coupled to the ability to phosphorylate H5, the only virus-encoded protein shown to be a B1 substrate in vivo. Expression of hVRK1 during nonpermissive ts2 infections restored virus production and plaque formation, whereas expression of mVRK1 resulted in an intermediate level of rescue. Taken together, these observations indicate that enzymatically active cellular VRK1 kinases can perform the function(s) of B1 required for genome replication, most likely due to overlapping specificity for cellular and/or viral substrates.

* Corresponding author. Mailing address: Dept. of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Rd., BSB-273, Milwaukee, WI 53226. Phone: (414) 456-8253. Fax: (414) 456-6535. E-mail: ptrakt{at}mcw.edu.

Journal of Virology, February 2004, p. 1992-2005, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1992-2005.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vigne, S., Duraffour, S., Andrei, G., Snoeck, R., Garin, D., Crance, J.-M. (2009). Inhibition of Vaccinia Virus Replication by Two Small Interfering RNAs Targeting B1R and G7L Genes and Their Synergistic Combination with Cidofovir. Antimicrob. Agents Chemother. 53: 2579-2588 [Abstract] [Full Text]  
  • Kang, T.-H., Park, D.-Y., Kim, W., Kim, K.-T. (2008). VRK1 phosphorylates CREB and mediates CCND1 expression. J. Cell Sci. 121: 3035-3041 [Abstract] [Full Text]  
  • Santos, C. R., Blanco, S., Sevilla, A., Lazo, P. A. (2006). Vaccinia Virus B1R Kinase Interacts with JIP1 and Modulates c-Jun-Dependent Signaling.. J. Virol. 80: 7667-7675 [Abstract] [Full Text]  
  • Nichols, R. J., Wiebe, M. S., Traktman, P. (2006). The Vaccinia-related Kinases Phosphorylate the N' Terminus of BAF, Regulating Its Interaction with DNA and Its Retention in the Nucleus. Mol. Biol. Cell 17: 2451-2464 [Abstract] [Full Text]  
  • Nichols, R. J., Traktman, P. (2004). Characterization of Three Paralogous Members of the Mammalian Vaccinia Related Kinase Family. J. Biol. Chem. 279: 7934-7946 [Abstract] [Full Text]  


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