Retinoic acid analogues inhibit human herpesvirus 8 replication.
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.
Caselli
Elisabetta
E
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Italy.
Galvan
Monica
M
Santoni
Fabio
F
Alvarez
Susana
S
de Lera
Angel R
AR
Ivanova
Diana
D
Gronemeyer
Hinrich
H
Caruso
Arnaldo
A
Guidoboni
Massimo
M
Cassai
Enzo
E
Dolcetti
Riccardo
R
Di Luca
Dario
D
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000821:virology; D004847:Epithelial Cells / Q000821:virology; D019288:Herpesvirus 8, Human / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D014212:Tretinoin