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| Status |
Public on Apr 30, 2008 |
| Title |
Human Herpesvirus-8 infection of pulmonary microvascular entdothelial cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Human herpesvirus-8 (HHV-8) is the causative agent of Kaposi’s sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). We have previously described evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH). We speculated that viral infection of the pulmonary microvascular endothelial cells could cause the angioproliferative phenotype characteristic of severe pulmonary arterial hypertension (PAH). We now demonstrate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells (HPMVECs) in vitro, confirming both latent and lytic infection. HHV-8 infection of HPMVECs resulted in significant changes of gene expression including alterations of pathways integral to both cellular apoptosis and angiogenesis. This infection also results in alterations of genes integral to the bone morphogenic protein (BMP) pathway, including down regulation of bone morphogenic protein receptor 1a (BMPR1a) and bone morphogenic protein 4 (BMP4). Other genes previously implicated in the development of PAH are also altered in expression by HHV-8 infection. These include increased expression of Interleukin-6 (IL-6) and the matrix metalloproteinases (MMP)-1, MMP-2 and MMP-10. Lastly, cells infected with HHV-8 apoptosis resistant. Infection of pulmonary microvascular endothelial cells with human herepesvirus-8 results in alteration of the BMP pathway as well as an anti-apoptotic phenotype, consistent with the development of plexiform lesions characteristic of pulmonary arterial hypertension.
Keywords: Viral infection of endothelial cells in culture
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| |
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| Overall design |
• Direct comparison of HHV8-infected and mock-infected human pulmonary microvascular endothelial cells.
• Triplicate infection and mock infection samples were prepared. One hybridization per sample, 6 total hybridizations
• Single channel hybridization (no reference).
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| |
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| Contributor(s) |
Bull TM, Meadows CA, Coldren CD, Moore MD, Nana-Sinkam SP, Campbell TB, Geraci MW |
| Citation(s) |
18587055 |
| Submission date |
Dec 08, 2006 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Christopher D Coldren |
| E-mail(s) |
Chris.Coldren@ucdenver.edu
|
| Phone |
303 724 6056
|
| Organization name |
University of Colorado School of Medicine
|
| Department |
Medicine
|
| Lab |
Pulmonary Sciences and Critical Care Medicine
|
| Street address |
12700 East 17th Place
|
| City |
Aurora |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA98663 |
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