Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells

Todd M. Bull, Christina A. Meadows, Christopher D. Coldren, Mark Moore, Sylk M. Sotto-Santiago, Serge P. Nana-Sinkam, Thomas B. Campbell, Mark W. Geraci

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)706-716
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume39
Issue number6
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Fingerprint

Herpesviridae Infections
Human Herpesvirus 8
Endothelial cells
Endothelial Cells
Lung
Apoptosis
Bone
Genes
Proteins
Polycyclic aromatic hydrocarbons
Viruses
Gene Expression
Gene expression
Primary Effusion Lymphoma
Bone and Bones
Culture Techniques
Kaposi's Sarcoma
Coculture Techniques
Infection
Pulmonary Hypertension

Keywords

  • Endothelial cells
  • HHV-8
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Bull, T. M., Meadows, C. A., Coldren, C. D., Moore, M., Sotto-Santiago, S. M., Nana-Sinkam, S. P., ... Geraci, M. W. (2008). Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells. American Journal of Respiratory Cell and Molecular Biology, 39(6), 706-716. https://doi.org/10.1165/rcmb.2007-0368OC

Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells. / Bull, Todd M.; Meadows, Christina A.; Coldren, Christopher D.; Moore, Mark; Sotto-Santiago, Sylk M.; Nana-Sinkam, Serge P.; Campbell, Thomas B.; Geraci, Mark W.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 39, No. 6, 01.12.2008, p. 706-716.

Research output: Contribution to journalArticle

Bull, TM, Meadows, CA, Coldren, CD, Moore, M, Sotto-Santiago, SM, Nana-Sinkam, SP, Campbell, TB & Geraci, MW 2008, 'Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells', American Journal of Respiratory Cell and Molecular Biology, vol. 39, no. 6, pp. 706-716. https://doi.org/10.1165/rcmb.2007-0368OC
Bull, Todd M. ; Meadows, Christina A. ; Coldren, Christopher D. ; Moore, Mark ; Sotto-Santiago, Sylk M. ; Nana-Sinkam, Serge P. ; Campbell, Thomas B. ; Geraci, Mark W. / Human herpesvirus-8 infection of primary pulmonary microvascular endothelial cells. In: American Journal of Respiratory Cell and Molecular Biology. 2008 ; Vol. 39, No. 6. pp. 706-716.
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