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.
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.
Authors: Megan M Goodwin; Jerome M Molleston; Susan Canny; Mohamed Abou El Hassan; Erin K Willert; Rod Bremner; Herbert W Virgin Journal: J Virol Date: 2010-08-18 Impact factor: 5.103
Authors: Kaitlin J Soye; Claire Trottier; Thomas Z Di Lenardo; Katherine H Restori; Lee Reichman; Wilson H Miller; Brian J Ward Journal: Virol J Date: 2013-11-14 Impact factor: 4.099
Authors: Ömer Faruk Elmas; Abdullah Demirbaş; Ömer Kutlu; Fatih Bağcıer; Mahmut Sami Metin; Kemal Özyurt; Necmettin Akdeniz; Mustafa Atasoy; Ümit Türsen; Torello Lotti Journal: Dermatol Ther Date: 2020-07-09 Impact factor: 3.858