U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis

Arnaldo Caruso, Elisabetta Caselli, Simona Fiorentini, Antonella Rotola, Alberto Prandini, Emirena Garrafa, Elisa Saba, Giulio Alessandri, Enzo Cassai, Dario Di Luca

Research output: Contribution to journalArticle

Abstract

Human herpesvirus 6 (HHV-6) is a lymphotropic virus, but recent observations showed that also vascular endothelial cells (ECs) are susceptible to infection, both in vivo and in vitro. The observation that lymph nodes are a site of viral persistence suggests that lymphatic ECs (LECs) might be even more relevant for HHV-6 biology than vascular ECs. Here,weprovide evidence that HHV-6 can infect LECs in vitro and establish a latent infection. Thus HHV-6 infection induces the loss of angiogenic properties both in LECs and in vascular ECs, as shown by the inability to form capillary-like structures and to seal wound scratches. The antiangiogenic effects observed in infected cells are associated to the expression of HHV-6 U94/rep, a latency-associated gene. In fact, transfection of U94/rep or addition of recombinant U94/REP protein to ECs inhibits the formation of in vitro capillary-like structures, reduces migration of ECs, and blocks angiogenesis, rendering rat aortic rings insensitive to VEGF-induced vasculogenetic activity. The ability of U94/rep to block different angiogenetic steps may lead to approaches in the potential control of the proliferation of blood and lymphatic vessels.

Original languageEnglish
Pages (from-to)20446-20451
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number48
DOIs
Publication statusPublished - Dec 1 2009

Keywords

  • Endothelial cells
  • Lymphatic endothelial cells

ASJC Scopus subject areas

  • General

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    Caruso, A., Caselli, E., Fiorentini, S., Rotola, A., Prandini, A., Garrafa, E., Saba, E., Alessandri, G., Cassai, E., & Di Luca, D. (2009). U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 106(48), 20446-20451. https://doi.org/10.1073/pnas.0905535106