Differential ligand binding to a human cytomegalovirus chemokine receptor determines cell type-specific motility

Jennifer Vomaske, Ryan M. Melnychuk, Patricia P. Smith, Joshua Powell, Laurel Hall, Victor De Filippis, Klaus Frueh, Martine Smit, David D. Schlaepfer, Jay Nelson, Daniel Streblow

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

While most chemokine receptors fail to cross the chemokine class boundary with respect to the ligands that they bind, the human cytomegalovirus (HCMV)-encoded chemokine receptor US28 binds multiple CC-chemokines and the CX3C-chemokine Fractalkine. US28 binding to CC-chemokines is both necessary and sufficient to induce vascular smooth muscle cell (SMC) migration in response to HCMV infection. However, the function of Fractalkine binding to US28 is unknown. In this report, we demonstrate that Fractalkine binding to US28 not only induces migration of macrophages but also acts to inhibit RANTES-mediated SMC migration. Similarly, RANTES inhibits Fractalkine-mediated US28 migration in macrophages. While US28 binding of both RANTES and Fractalkine activate FAK and ERK-1/2, RANTES signals through Gα12 and Fractalkine through Gαq. These findings represent the first example of differential chemotactic signaling via a multiple chemokine family binding receptor that results in migration of two different cell types. Additionally, the demonstration that US28-mediated chemotaxis is both ligand-specific and cell type-specific has important implications in the role of US28 in HCMV pathogenesis.

Original languageEnglish (US)
Article numbere1000304
JournalPLoS Pathogens
Volume5
Issue number2
DOIs
StatePublished - Feb 2009

Fingerprint

Chemokine CX3CL1
Chemokine Receptors
Cell Movement
Chemokine CCL5
Ligands
CC Chemokines
Cytomegalovirus
Chemokines
Smooth Muscle Myocytes
CX3C Chemokines
Macrophages
Cytomegalovirus Infections
Chemotaxis
Vascular Smooth Muscle
cytomegalovirus receptor

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

Differential ligand binding to a human cytomegalovirus chemokine receptor determines cell type-specific motility. / Vomaske, Jennifer; Melnychuk, Ryan M.; Smith, Patricia P.; Powell, Joshua; Hall, Laurel; De Filippis, Victor; Frueh, Klaus; Smit, Martine; Schlaepfer, David D.; Nelson, Jay; Streblow, Daniel.

In: PLoS Pathogens, Vol. 5, No. 2, e1000304, 02.2009.

Research output: Contribution to journalArticle

Vomaske, Jennifer ; Melnychuk, Ryan M. ; Smith, Patricia P. ; Powell, Joshua ; Hall, Laurel ; De Filippis, Victor ; Frueh, Klaus ; Smit, Martine ; Schlaepfer, David D. ; Nelson, Jay ; Streblow, Daniel. / Differential ligand binding to a human cytomegalovirus chemokine receptor determines cell type-specific motility. In: PLoS Pathogens. 2009 ; Vol. 5, No. 2.
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