Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation.
The mechanism of the antiviral activity of hypericin was characterized and compared with that of rose bengal. Both compounds inactivate enveloped (but not unenveloped) viruses upon illumination by visible light. Human immunodeficiency and vesicular stomatitis viruses were photodynamically inactivated by both dyes at nanomolar concentrations. Photodynamic inactivation of fusion (hemolysis) by vesicular stomatitis, influenza, and Sendai viruses was induced by both dyes under similar conditions (e.g., I50 = 20-50 nM for vesicular stomatitis virus), suggesting that loss of infectivity resulted from inactivation of fusion. Syncytium formation, between cells activated to express human immunodeficiency virus gp120 on their surfaces and CD4+ cells, was inhibited by illumination in the presence of 1 microM hypericin. Hypericin and rose bengal thus exert similar virucidal effects. Both presumably act by the same mechanism--namely, the inactivation of the viral fusion function by singlet oxygen produced upon illumination. The implications of this photodynamic antiviral action for the potential therapeutic usefulness of both hypericin and rose bengal are discussed.
Lenard
J
J
Department of Physiology and Biophysics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854-5635.
Rabson
A
A
Vanderoef
R
R
D000818:Animals; D000873:Anthracenes; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D015726:Giant Cells / Q000187:drug effects*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D007700:Kinetics; D008027:Light; D008214:Lymphocytes / Q000187:drug effects / Q000382:microbiology; D008561:Membrane Fusion / Q000187:drug effects*; D010222:Parainfluenza Virus 1, Human / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012395:Rose Bengal / Q000494:pharmacology*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology
D000873:Anthracenes; D000998:Antiviral Agents; D011838:Radiation-Sensitizing Agents; D012395:Rose Bengal; D010569:Perylene; C004965:hypericin; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase