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 Melnychuk, R. M.
Right arrow Articles by Streblow, D. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Melnychuk, R. M.
Right arrow Articles by Streblow, D. N.

 Previous Article  |  Next Article 

Journal of Virology, August 2005, p. 10788-10795, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10788-10795.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mouse Cytomegalovirus M33 Is Necessary and Sufficient in Virus-Induced Vascular Smooth Muscle Cell Migration

Ryan M. Melnychuk,1 Patsy Smith,1 Craig N. Kreklywich,1,2,4 Franziska Ruchti,1 Jennifer Vomaske,1 Laurel Hall,1 Lambert Loh,5 Jay A. Nelson,1,3 Susan L. Orloff,1,2,4 and Daniel N. Streblow1,3*

Department of Molecular Microbiology and Immunology,1 Department of Surgery,2 Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Portland, Oregon 97239,3 Portland VA Medical Center, Portland, Oregon 97239,4 Department of Microbiology, University of Saskatchewan, Saskatoon, Saskatchewan 57N 5E5, Canada5

Received 8 December 2004/ Accepted 4 May 2005

Mouse cytomegalovirus (MCMV) encodes two potential seven-transmembrane-spanning proteins with homologies to cellular chemokine receptors, M33 and M78. While these virus-encoded chemokine receptors are necessary for the in vivo pathogenesis of MCMV, the function of these proteins is unknown. Since vascular smooth muscle cell (SMC) migration is of critical importance for the development of atherosclerosis and other vascular diseases, the ability of M33 to promote SMC motility was assessed. Similar to human CMV, MCMV induced the migration of mouse aortic SMCs but not mouse fibroblasts. To demonstrate whether M33 was required for MCMV-induced SMC migration, we employed interfering-RNA technology to specifically knock down M33 expression in the context of viral infection. The knockdown of M33 resulted in the specific reduction of M33 protein expression and ablation of MCMV-mediated SMC migration but failed to reduce viral growth in cultured cells. Adenovirus vector expression of M33 was sufficient to promote SMC migration, which was enhanced in the presence of recombinant mouse RANTES (mRANTES). In addition, M33 promoted the activation of Rac1 and extracellular signal-related kinase 1/2 upon stimulation with mRANTES. These findings demonstrate that mRANTES is a ligand for this chemokine receptor and that the activation of M33 occurs in a ligand-dependent manner. Thus, M33 is a functional homologue of US28 that is required for MCMV-induced vascular SMC migration.

* Corresponding author. Mailing address: Oregon Health Sciences University, Vaccine and Gene Therapy Institute, Beaverton, OR 97006. Phone: (503) 418-4038. Fax: (503) 418-2719. E-mail: streblow{at}ohsu.edu.

Journal of Virology, August 2005, p. 10788-10795, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10788-10795.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Maussang, D., Vischer, H. F., Leurs, R., Smit, M. J. (2009). Herpesvirus-Encoded G Protein-Coupled Receptors as Modulators of Cellular Function. Mol. Pharmacol. 76: 692-701 [Abstract] [Full Text]  
  • Cardin, R. D., Schaefer, G. C., Allen, J. R., Davis-Poynter, N. J., Farrell, H. E. (2009). The M33 Chemokine Receptor Homolog of Murine Cytomegalovirus Exhibits a Differential Tissue-Specific Role during In Vivo Replication and Latency. J. Virol. 83: 7590-7601 [Abstract] [Full Text]  
  • Case, R., Sharp, E., Benned-Jensen, T., Rosenkilde, M. M., Davis-Poynter, N., Farrell, H. E. (2008). Functional Analysis of the Murine Cytomegalovirus Chemokine Receptor Homologue M33: Ablation of Constitutive Signaling Is Associated with an Attenuated Phenotype In Vivo. J. Virol. 82: 1884-1898 [Abstract] [Full Text]  
  • Krebs, P., Scandella, E., Bolinger, B., Engeler, D., Miller, S., Ludewig, B. (2007). Chronic Immune Reactivity Against Persisting Microbial Antigen in the Vasculature Exacerbates Atherosclerotic Lesion Formation. Arterioscler. Thromb. Vasc. Bio. 27: 2206-2213 [Abstract] [Full Text]  
  • Tadagaki, K., Yamanishi, K., Mori, Y. (2007). Reciprocal roles of cellular chemokine receptors and human herpesvirus 7-encoded chemokine receptors, U12 and U51. J. Gen. Virol. 88: 1423-1428 [Abstract] [Full Text]  
  • Sherrill, J. D., Miller, W. E. (2006). G Protein-coupled Receptor (GPCR) Kinase 2 Regulates Agonist-independent Gq/11 Signaling from the Mouse Cytomegalovirus GPCR M33. J. Biol. Chem. 281: 39796-39805 [Abstract] [Full Text]  
  • Pinto, A. K., Munks, M. W., Koszinowski, U. H., Hill, A. B. (2006). Coordinated Function of Murine Cytomegalovirus Genes Completely Inhibits CTL Lysis.. J. Immunol. 177: 3225-3234 [Abstract] [Full Text]  
  • Froberg, M. K., Dannen, D., Adams, A., Parker-Thornburg, J., Kolattukudy, P. (2006). Murine Cytomegalovirus Infection Markedly Reduces Serum MCP-1 Levels in MCP-1 Transgenic Mice.. Annals of Clinical & Laboratory Science 36: 179-184 [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»