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

Authors

Ryan Melnychuk, Oregon Health Sciences University
Patsy Smith, Oregon Health Sciences University
Craig N. Kreklywich, Oregon Health Sciences University
Franziska Ruchti, Oregon Health Sciences University
Jennifer Totonchy, Chapman UniversityFollow
Laurel Hall, Oregon Health Sciences University
Lambert Loh, University of Saskatchewan
Jay A. Nelson, Oregon Health Sciences University
Susan L. Orloff, Oregon Health Sciences University
Daniel N. Streblow, Oregon Health Sciences University

Document Type

Article

Publication Date

2005

Abstract

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.

Comments

This article was originally published in Journal of Virology, volume 79, issue 16, in 2005. DOI: 10.1128/JVI.79.16.10788-10795.2005

Recommended Citation

Melnychuk RM, Smith P, Kreklywich CN, et al. Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration. Journal of Virology. 2005;79(16):10788-10795. doi:10.1128/JVI.79.16.10788-10795.2005.

Copyright

American Society for Microbiology