Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells.

Bull TM, Meadows CA, Coldren CD, Moore M, Sotto-Santiago SM, Nana-Sinkam SP, Campbell TB, Geraci MW
Am J Respir Cell Mol Biol. 2008 39 (6): 706-16

PMID: 18587055 · PMCID: PMC2586046 · DOI:10.1165/rcmb.2007-0368OC

Human herpesvirus-8 (HHV-8) is the causative agent of Kaposi's sarcoma and is associated with the angioproliferative disorders primary effusion lymphoma and multicentric Castleman's disease. Evidence of HHV-8 infection within the pulmonary vasculature of patients with idiopathic pulmonary arterial hypertension (IPAH) has been described. We hypothesize that HHV-8 infection of pulmonary microvascular endothelial cells results in an apoptotic-resistant phenotype characteristic of severe pulmonary arterial hypertension. Our objective was to investigate the ability of HHV-8 to infect human pulmonary microvascular endothelial cells in vitro and characterize the phenotypic effect of this infection. Human pulmonary microvascular endothelial cells were exposed to HHV-8 using two methods (direct virus and co-culture technique). The presence of lytic and latent infection was confirmed. Changes in endothelial cell gene and protein expression and effects on cellular apoptosis were measured. HHV-8 can both lytically and latently infect primary human pulmonary microvascular endothelial cells in vitro. HHV-8 infection results in significant changes in gene expression, including alterations of pathways important to cellular apoptosis. HHV-8 infection also alters expression of genes integral to the bone morphogenic protein pathway, including down-regulation of bone morphogenic protein-4. Other genes previously implicated in the development of PAH are affected by HHV-8 infection, and cells infected with HHV-8 are resistant to apoptosis.

MeSH Terms (20)

Apoptosis Blood Vessels Bone Morphogenetic Protein 4 Carrier Proteins Caspase 3 Caspase 7 Cells, Cultured Culture Media, Conditioned Endothelial Cells Enzyme-Linked Immunosorbent Assay Fluorescent Antibody Technique Gene Expression Regulation Herpesviridae Infections Herpesvirus 8, Human In Situ Nick-End Labeling Interleukin-6 Oligonucleotide Array Sequence Analysis Phenotype Polymerase Chain Reaction Reproducibility of Results

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