MECHANISMS OF HCMV-US28 VASCULAR SMOOTH MUSCLE CELL MIGR

Project: Research project

Description

DESCRIPTION The long-term goal of this project is to define the role of human cytomegalovirus (HCMV) in the development of vascular diseases, including atherosclerosis. HCMV has been previously linked to the development of vascular diseases, although it remains to fully elucidate if its contribution is by direct injection or via indirect mechanisms. Previous studies have suggested that vascular smooth muscle cell (vSMC) migration is a crucial factor in the development of many vascular diseases. HCMV infected SMC have been found within the intima of the earliest detectable human atherosclerotic lesions. These findings suggest the hypothesis that infection of vSMC can promote the development of vascular disease by direct mechanisms or indirectly by enhancing production of growth factors that promote the atherosclerotic disease process. Recently, we in Dr. Nelson's laboratory have determined that in vitro HCMV infection of vSMC induces a phenotype that causes these cells to migrate through a transwell system. Migration is cell-type specific and only occurs in arterial SMC and not HCMV infected venous SMC, endothelial cells of fibroblasts. The HCMV-induced SMC migration is dependent upon expression of the HCMV-encoded chemokine receptor US28. Indeed, US28 is necessary and sufficient to induce migration of these cells, although the mechanisms by which this occurs is still unknown. The aim of this proposal is to determine the mechanisms by which the HCMV-encoded chemokine receptor US28 induces SMC migration defining the function domains of US28 required for induction of SMC migration and the US28-coupled signaling pathways.
StatusActive
Effective start/end date3/1/00 → …

Funding

  • National Institutes of Health: $37,516.00

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Cytomegalovirus
Vascular Smooth Muscle
Smooth Muscle Myocytes
Vascular Diseases
Cell Movement
Chemokine Receptors
Cytomegalovirus Infections
Atherosclerosis
Intercellular Signaling Peptides and Proteins
Endothelial Cells
Fibroblasts
Phenotype
Injections
Infection

Keywords

  • Medicine(all)
  • Immunology and Microbiology(all)