Antiviral Activity of a Bile Pigment, Biliverdin, against Human Herpesvirus 6 (HHV‐6) In Vitro

Abstract

Biliverdin (BV

Bilirubin: An Endogenous Molecule with Antiviral Activity in vitro

“…Biliverdin-IX-alpha was shown to inhibit the replication of HCV, HHV-6, and HIV (Mori et al, 1991; Nakagami et al, 1992; Lehmann et al, 2010; Zhu et al, 2010), CO reduced the growth of E. coli , P. aeruginosa , and S. aureus (Nobre et al, 2007, 2009; Davidge et al, 2009; Desmard et al, 2012) and iron almost completely decreased HCV core mRNA and protein (Hou et al, 2009). The results shown in this paper provided original evidence about the antiviral role of BR, the formation of which requires the concerted action of both HO and BVR, thus expanding the cytoprotective role of this linear tetrapyrrole.…”

“…Almost all organs retain BVR activity which transforms BV into BR (Maines, 1997, 2005). That said, it is plausible to wonder whether or not the antiviral activity of BV against HHV-6, HIV, or HCV (Mori et al, 1991; Nakagami et al, 1992; Lehmann et al, 2010; Zhu et al, 2010) should be attributable to its conversion into BR by the MT-4 or Huh cells used in those studies rather than a distinct effect of BV. The lack of inactivation of HHV-6 virions by BV and the consequent reduced antiviral effect lend support to this hypothesis.…”

“…The lack of inactivation of HHV-6 virions by BV and the consequent reduced antiviral effect lend support to this hypothesis. Another concern raised from the studies by Nakagami et al (1992) and Mori et al (1991) is related to the concentrations of BV used to inhibit HHV-6 and HIV replication. In these studies the antiviral effect of BV was observed at concentrations ranging from 10 to 66.7 μg/ml, equivalent to ∼17 and 113 μM, respectively, two values much higher than those expected to be produced by the HO activity in humans (Coburn, 1970).…”

“…The overexpression of the inducible isoform of HO (HO-1) displayed a significant antiviral activity against enterovirus and hepatitis viruses (Zhu et al, 2010; Tung et al, 2011). With regard to the by-products of the HO system involved in this antiviral activity, BV was shown to interfere with human hepatitis C virus (HCV) and human herpes virus (HHV)-6 replication as well as to reduce the cytopathic effect of human immunodeficiency type 1 virus (HIV) in Huh or MT-4 cells (Mori et al, 1991; Nakagami et al, 1992; Lehmann et al, 2010; Zhu et al, 2010). In addition, CO inhibited the growth of enterovirus, E. coli , P. aeruginosa as well as S. aureus (Nobre et al, 2007; Tung et al, 2011; Desmard et al, 2012) and iron almost completely decreased HCV core mRNA and protein (Hou et al, 2009).…”

Bilitrienones from the chemical oxidation of dodecasubstituted porphyrins

“…The open-chain oxygenated tetrapyrroles, often designated generically as bile pigments, perform important biological functions, for example as the chromophores in biliproteins,4–6 and have been proposed for various applications, including as antiviral and antioxidant agents 7–9. In living organisms, bile pigments (e. g. biliverdins) are formed from the highly specific enzymatic oxidation of heme, catalyzed by heme oxygenase 10,11.…”