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Journal Articles Antiviral Therapy Year : 2008

Retinoic acid analogues inhibit human herpesvirus 8 replication

Elisabetta Caselli
  • Function : Author
Monica Galvan
  • Function : Author
Fabio Santoni
  • Function : Author
Susana Alvarez
  • Function : Author
Angel R. de Lera
  • Function : Author
Diana Ivanova
  • Function : Author
Arnaldo Caruso
  • Function : Author
Massimo Guidoboni
  • Function : Author
Enzo Cassai
  • Function : Author
Riccardo Dolcetti
  • Function : Author
Dario Di Luca
  • Function : Author

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.
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hal-04108311 , version 1 (26-05-2023)

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Elisabetta Caselli, Monica Galvan, Fabio Santoni, Susana Alvarez, Angel R. de Lera, et al.. Retinoic acid analogues inhibit human herpesvirus 8 replication. Antiviral Therapy, 2008, 13 (2), pp.199-209. ⟨10.1177/1359653508013002⟩. ⟨hal-04108311⟩
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