Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration

Ryan M. Melnychuk, Patsy Smith, Craig N. Kreklywich, Franziska Ruchti, Jennifer Vomaske, Laurel Hall, Lambert Loh, Jay Nelson, Susan Orloff, Daniel Streblow

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 flbroblasts. 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.

Original languageEnglish (US)
Pages (from-to)10788-10795
Number of pages8
JournalJournal of Virology
Volume79
Issue number16
DOIs
StatePublished - Aug 2005

Fingerprint

Murid herpesvirus 1
Muromegalovirus
Vascular Smooth Muscle
cell movement
blood vessels
smooth muscle
myocytes
Smooth Muscle Myocytes
Cell Movement
Viruses
Chemokine CCL5
viruses
Chemokine Receptors
mice
Ligands
vascular diseases
Proteins
transmembrane proteins
Adenoviridae
Virus Diseases

ASJC Scopus subject areas

  • Immunology

Cite this

Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration. / Melnychuk, Ryan M.; Smith, Patsy; Kreklywich, Craig N.; Ruchti, Franziska; Vomaske, Jennifer; Hall, Laurel; Loh, Lambert; Nelson, Jay; Orloff, Susan; Streblow, Daniel.

In: Journal of Virology, Vol. 79, No. 16, 08.2005, p. 10788-10795.

Research output: Contribution to journalArticle

Melnychuk, Ryan M. ; Smith, Patsy ; Kreklywich, Craig N. ; Ruchti, Franziska ; Vomaske, Jennifer ; Hall, Laurel ; Loh, Lambert ; Nelson, Jay ; Orloff, Susan ; Streblow, Daniel. / Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration. In: Journal of Virology. 2005 ; Vol. 79, No. 16. pp. 10788-10795.
@article{dbb21d470fae44ddb96b797d96bb6022,
title = "Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration",
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 flbroblasts. 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.",
author = "Melnychuk, {Ryan M.} and Patsy Smith and Kreklywich, {Craig N.} and Franziska Ruchti and Jennifer Vomaske and Laurel Hall and Lambert Loh and Jay Nelson and Susan Orloff and Daniel Streblow",
year = "2005",
month = "8",
doi = "10.1128/JVI.79.16.10788-10795.2005",
language = "English (US)",
volume = "79",
pages = "10788--10795",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "16",

}

TY - JOUR

T1 - Mouse cytomegalovirus M33 is necessary and sufficient in virus-induced vascular smooth muscle cell migration

AU - Melnychuk, Ryan M.

AU - Smith, Patsy

AU - Kreklywich, Craig N.

AU - Ruchti, Franziska

AU - Vomaske, Jennifer

AU - Hall, Laurel

AU - Loh, Lambert

AU - Nelson, Jay

AU - Orloff, Susan

AU - Streblow, Daniel

PY - 2005/8

Y1 - 2005/8

N2 - 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 flbroblasts. 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.

AB - 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 flbroblasts. 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.

UR - http://www.scopus.com/inward/record.url?scp=23244436447&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23244436447&partnerID=8YFLogxK

U2 - 10.1128/JVI.79.16.10788-10795.2005

DO - 10.1128/JVI.79.16.10788-10795.2005

M3 - Article

VL - 79

SP - 10788

EP - 10795

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 16

ER -