Retinoic acid analogues inhibit human herpesvirus 8 replication

Elisabetta Caselli, Monica Galvan, Fabio Santoni, Susana Alvarez, Angel R. De Lera, Diana Ivanova, Hinrich Gronemeyer, Arnaldo Caruso, Massimo Guidoboni, Enzo Cassai, Riccardo Dolcetti, Dario Di Luca

Research output: Contribution to journalArticle

Abstract

Background: Retinoids have a pronounced antiviral effect against several viruses. In this study we aimed to investigate the effect of retinoids on human herpesvirus 8 (HHV-8). Methods: A panel of retinoic acid compounds were tested for their antiviral activity against HHV-8 in human umbilical vascular endothelial cells (HUVECs) and in a human epithelial cell line. The presence, transcription and antigen expression of HHV-8 in infected cells - in the presence or absence of retinoic acid compounds - were evaluated by PCR, reverse transcriptase PCR and immunofluorescence assays; HHV-8 viral load was determined by real-time quantitative PCR. Angiogenesis induced by HHV-8 was also assessed using Cultrex® basement membrane extract. Results: The compounds tested specifically inhibited viral promoters, during the early and late phases of infection in both cell systems tested, and resulted in up to 100-fold reduction of viral titre and release of progeny virus. The inhibition of viral replication induced by retinoids in endothelial cells, the primary target of HHV-8-driven transformation in Kaposi's Sarcoma, prevented endothelial cells from developing spindle morphology and in vitro tube formation, characteristic changes associated with HHV-8 infection and transformation. Conclusions: We show that retinoids inhibit HHV-8 replication and identify new retinoid compounds with a strong antiviral effect. Selective retinoids, particularly those with retinoic acid receptor agonist activity, may be good candidates for the development of antiviral drugs.

Original languageEnglish
Pages (from-to)199-209
Number of pages11
JournalAntiviral Therapy
Volume13
Issue number2
Publication statusPublished - 2008

ASJC Scopus subject areas

  • Pharmacology

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    Caselli, E., Galvan, M., Santoni, F., Alvarez, S., De Lera, A. R., Ivanova, D., Gronemeyer, H., Caruso, A., Guidoboni, M., Cassai, E., Dolcetti, R., & Di Luca, D. (2008). Retinoic acid analogues inhibit human herpesvirus 8 replication. Antiviral Therapy, 13(2), 199-209.