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Title: Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing

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.

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
937364
Report Number(s):
PNNL-SA-60994
Journal ID: ISSN 0022-538X; JOVIAM; 24698; 400412000; TRN: US200819%%93
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of Virology, 82(13):6524-6535
Additional Journal Information:
Journal Volume: 82; Journal Issue: 13; Journal ID: ISSN 0022-538X
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ACCELERATION; FUNCTIONALS; GROWTH FACTORS; HEALING; HERPES SIMPLEX; INDUCTION; LYMPHOKINES; MASS SPECTROSCOPY; ORGANS; PROTEINS; SECRETION; STABILIZATION; TRANSPLANTS; VASCULAR DISEASES; WOUNDS; Environmental Molecular Sciences Laboratory

Citation Formats

Dumortier, Jerome, Streblow, Daniel N, Moses, Ashlee V, Jacobs, Jon M, Kreklywich, Craig N, Camp, David G, Smith, Richard D, Orloff, Susan L, and Nelson, Jay. Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing. United States: N. p., 2008. Web. doi:10.1128/JVI.00502-08.
Dumortier, Jerome, Streblow, Daniel N, Moses, Ashlee V, Jacobs, Jon M, Kreklywich, Craig N, Camp, David G, Smith, Richard D, Orloff, Susan L, & Nelson, Jay. Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing. United States. https://doi.org/10.1128/JVI.00502-08
Dumortier, Jerome, Streblow, Daniel N, Moses, Ashlee V, Jacobs, Jon M, Kreklywich, Craig N, Camp, David G, Smith, Richard D, Orloff, Susan L, and Nelson, Jay. 2008. "Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing". United States. https://doi.org/10.1128/JVI.00502-08.
@article{osti_937364,
title = {Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing},
author = {Dumortier, Jerome and Streblow, Daniel N and Moses, Ashlee V and Jacobs, Jon M and Kreklywich, Craig N and Camp, David G and Smith, Richard D and Orloff, Susan L and Nelson, Jay},
abstractNote = {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.},
doi = {10.1128/JVI.00502-08},
url = {https://www.osti.gov/biblio/937364}, journal = {Journal of Virology, 82(13):6524-6535},
issn = {0022-538X},
number = 13,
volume = 82,
place = {United States},
year = {Tue Jul 01 00:00:00 EDT 2008},
month = {Tue Jul 01 00:00:00 EDT 2008}
}