Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing

Jerome Dumortier, Daniel Streblow, Ashlee Moses, Jon M. Jacobs, Craig N. Kreklywich, David Camp, Richard D. Smith, Susan Orloff, Jay Nelson

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) is implicated in the acceleration of a number of vascular diseases including transplant vascular sclerosis (TVS), the lesion associated with chronic rejection (CR) of solid organ transplants. Although the virus persists in the allograft throughout the course of disease, few cells are directly infected by CMV. This observation is in contrast to the global effects that CMV has on the acceleration of TVS/CR, suggesting that CMV infection indirectly promotes the vascular disease process. Recent transcriptome analysis of CMV-infected heart allografts indicates that the virus induces cytokines and growth factors associated with angiogenesis (AG) and wound healing (WH), suggesting that CMV may accelerate TVS/CR through the induction and secretion of AG/WH factors from infected cells. We analyzed virus-free supernatants from HCMV-infected cells (HCMV secretomes) for growth factors, by mass spectrometry and immunoassays, and found that the HCMV secretome contains over 1,000 cellular proteins, many of which are involved in AG/WH. Importantly, functional assays demonstrated that CMV but not herpes simplex virus secretomes not only induce AG/WH but also promote neovessel stabilization and endothelial cell survival for 2 weeks. These findings suggest that CMV acceleration of TVS occurs through virus-induced growth factors and cytokines in the CMV secretome.

Original languageEnglish (US)
Pages (from-to)6524-6535
Number of pages12
JournalJournal of Virology
Volume82
Issue number13
DOIs
StatePublished - Jul 2008

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Human herpesvirus 5
Angiogenesis Inducing Agents
angiogenesis
tissue repair
Cytomegalovirus
Wound Healing
Arteriosclerosis
sclerosis
blood vessels
Transplants
viruses
growth factors
Viruses
Intercellular Signaling Peptides and Proteins
vascular diseases
allografting
Vascular Diseases
Allografts
cytokines
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing. / Dumortier, Jerome; Streblow, Daniel; Moses, Ashlee; Jacobs, Jon M.; Kreklywich, Craig N.; Camp, David; Smith, Richard D.; Orloff, Susan; Nelson, Jay.

In: Journal of Virology, Vol. 82, No. 13, 07.2008, p. 6524-6535.

Research output: Contribution to journalArticle

Dumortier, Jerome ; Streblow, Daniel ; Moses, Ashlee ; Jacobs, Jon M. ; Kreklywich, Craig N. ; Camp, David ; Smith, Richard D. ; Orloff, Susan ; Nelson, Jay. / Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing. In: Journal of Virology. 2008 ; Vol. 82, No. 13. pp. 6524-6535.
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