Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8

Ashlee Moses, Kenneth N. Fish, Rebecca Ruhl, Patricia P. Smith, Joanne G. Strussenberg, Liangjin Zhu, Bala Chandran, Jay Nelson

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

Human herpesvirus 8 (HHV8) infects Kaposi's sarcoma (KS) spindle cells in situ, as well as the lesional endothelial cells considered to be spindle cell precursors. The HHV8 genome contains several oncogenes, suggesting that infection of endothelial and spindle cells could induce cellular transformation and tumorigenesis and promote the formation of KS lesions. To investigate the potential of HHV8 infection of endothelial cells to contribute to the development of KS, we have developed an in vitro model utilizing dermal microvascular endothelial cells that support significant HHV8 infection. In contrast to existing in vitro systems used to study HHV8 pathogenesis, the majority of dermal endothelial cells are infected with HHV8 and the viral genome is maintained indefinitely. Infection is predominantly latent, with a small percentage of cells supporting lyric replication, and latency is responsive to lyric induction stimuli. Infected endothelial cells develop a spindle shape resembling that of KS lesional cells and show characteristics of a transformed phenotype, including loss of contact inhibition and acquisition of anchorage-independent growth. These results describe a relevant model system in which to study virus-host interactions in vitro and demonstrate the ability of HHV8 to induce phenotypic changes in infected endothelial cells that resemble characteristics of KS spindle cells in vivo. Thus, our results are consistent with a direct role for HHV8 in the pathogenesis of KS.

Original languageEnglish (US)
Pages (from-to)6892-6902
Number of pages11
JournalJournal of Virology
Volume73
Issue number8
StatePublished - 1999

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Human herpesvirus 8
Human Herpesvirus 8
endothelial cells
Kaposi's Sarcoma
sarcoma
Endothelial Cells
Skin
Infection
infection
Herpesviridae Infections
cells
pathogenesis
Contact Inhibition
genome
Viral Genome
oncogenes
Oncogenes
carcinogenesis
Carcinogenesis
Genome

ASJC Scopus subject areas

  • Immunology

Cite this

Moses, A., Fish, K. N., Ruhl, R., Smith, P. P., Strussenberg, J. G., Zhu, L., ... Nelson, J. (1999). Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8. Journal of Virology, 73(8), 6892-6902.

Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8. / Moses, Ashlee; Fish, Kenneth N.; Ruhl, Rebecca; Smith, Patricia P.; Strussenberg, Joanne G.; Zhu, Liangjin; Chandran, Bala; Nelson, Jay.

In: Journal of Virology, Vol. 73, No. 8, 1999, p. 6892-6902.

Research output: Contribution to journalArticle

Moses, A, Fish, KN, Ruhl, R, Smith, PP, Strussenberg, JG, Zhu, L, Chandran, B & Nelson, J 1999, 'Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8', Journal of Virology, vol. 73, no. 8, pp. 6892-6902.
Moses, Ashlee ; Fish, Kenneth N. ; Ruhl, Rebecca ; Smith, Patricia P. ; Strussenberg, Joanne G. ; Zhu, Liangjin ; Chandran, Bala ; Nelson, Jay. / Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8. In: Journal of Virology. 1999 ; Vol. 73, No. 8. pp. 6892-6902.
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