3-O-METHYLFUNICONE, A FUNGAL METABOLITE PRODUCED BY TALAROMYCES PINOPHILUS, AS POTENTIAL ANTIVIRAL IN BOVINE HERPESVIRUS 1 INFECTION, THROUGH MODULATION OF ARYL HYDROCARBON RECEPTOR

Objectives: Bovine herpesvirus 1 (BoHV-1), a pathogen of cattle, can provoke infectious bovine rhinotracheitis, conjunctivitis and abortion. Due to its immunosuppressive properties, it is also a cofactor for bovine respiratory disease complex, an inflammatory disease responsible of pneumonia and death. Recent evidence indicates that some agonists of the aryl hydrocarbon receptor (AhR) may improve the host response to herpesviruses infection. Currently, antiviral compounds against BoHV-1 infection are often accompanied by toxic activity. Interestingly, some secondary metabolites, produced by the species Talaromyces pinophilus, like 3-O-methylfunicone (3-OMF) display considerable antiviral properties. Indeed, sulochrin and analogues, such as 3-OMF, decrease the infectivity of hepatitis C virus. Thus, in this study we assessed the property of 3-OMF in BoHV-1 infection. Methods used: Infection of BoHV-1 (Cooper strain) in MDBK cells, in co-treatment with 3-OMF (obtained by extraction and chromatographic purification of culture filtrate of T. piniphilus, strain LT6) was performed. In vitro bioscreen, cytomorphological and immunofluorescence analyses were carried out. Results: During BoHV-1 infection, the non-toxic concentration of 5 M 3-OMF reduced noticeably cell death signs and increased cell proliferation. Furthermore, 3-OMF induced a significant decrease in cytopathic effects, accompanied by the inhibition of the expression of bICP0, the major regulatory protein in lytic cycle of BoHV-1. In addition, 3-OMF up-regulated considerably the expression of AhR during infection. Conclusions: Taken together, our results suggest that 3-OMF, involving AhR, shows potential properties against BoHV-1 infection. Further studies are needed to elucidate the mechanisms by which targeting AhR may become a new approach for antiviral treatment.