Human herpesvirus-6 modulates RANTES production in primary human endothelial cell cultures

Arnaldo Caruso, Flavia Favilli, Antonella Rotola, Manola Comar, Douglas Horejsh, Giulio Alessandri, Manuela Grassi, Dario Di Luca, Simona Fiorentini

Research output: Contribution to journalArticlepeer-review

Abstract

Human herpesvirus 6 (HHV6) is a beta-herpesvirus capable of infecting several cell types from different origins. HHV6 is the etiological agent of exantem subitum and has been associated with several diseases, all characterized by an inflammatory response triggered by chemokines. We show that strain U1102 of HHV6 is able to infect persistently human endothelial cells obtained from umbilical veins, adult aorta and adult heart microvessels, without apparent cytopathic effect. Analysis by in situ PCR showed that HHV6 sequences were present in 20% of HUVEC, 10% of aortic, and 1% of heart microvascular endothelial cells. Regardless of endothelial cell origin, HHV6 infection induced de novo synthesis of the RANTES CC-chemokine. It was found, however, that microvascular endothelial cells, despite their lower susceptibility to HHV6 infection, showed the highest RANTES expression. Chemokine production occurred also in the absence of viral DNA synthesis. Furthermore, RANTES synthesis required an active viral genome, as UV-inactivated HHV6 infection of endothelial cells did not lead to chemokine production. We investigated the expression of HHV6 U51 gene, which encodes a chemokine receptor that is already known to sequester and down modulate RANTES in epithelial cells. HHV6-infected endothelial cells coexpressed RANTES and U51 mRNAs starting from 12 hr up to 48 hr post-infection. Then, RANTES transcripts disappeared whereas U51 messages continued to be expressed. In conclusion, this study highlights the major role of HHV6 in endothelial cell biology and the development of inflammatory processes.

Original languageEnglish
Pages (from-to)451-458
Number of pages8
JournalJournal of Medical Virology
Volume70
Issue number3
DOIs
Publication statusPublished - Jul 1 2003

Keywords

  • Aorta
  • Endothelial cells
  • Human herpesvirus 6
  • HUVEC
  • RANTES

ASJC Scopus subject areas

  • Virology

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