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. 1993 Jan 1;90(1):158–162. doi: 10.1073/pnas.90.1.158

Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation.

J Lenard 1, A Rabson 1, R Vanderoef 1
PMCID: PMC45619  PMID: 7678335

Abstract

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.

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Selected References

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  1. Andersen D. O., Weber N. D., Wood S. G., Hughes B. G., Murray B. K., North J. A. In vitro virucidal activity of selected anthraquinones and anthraquinone derivatives. Antiviral Res. 1991 Sep;16(2):185–196. doi: 10.1016/0166-3542(91)90024-l. [DOI] [PubMed] [Google Scholar]
  2. Bailey C. A., Miller D. K., Lenard J. Effects of DEAE-dextran on infection and hemolysis by VSV. Evidence that nonspecific electrostatic interactions mediate effective binding of VSV to cells. Virology. 1984 Feb;133(1):111–118. doi: 10.1016/0042-6822(84)90429-x. [DOI] [PubMed] [Google Scholar]
  3. Barratt M. D., Evans J. C., Lewis C. A., Rowlands C. C. Comparison of the photodynamic action of Rose Bengal and tetrachlorosalicylanilide on isolated porcine erythrocyte membranes. Chem Biol Interact. 1982 Jan;38(2):215–230. doi: 10.1016/0009-2797(82)90041-2. [DOI] [PubMed] [Google Scholar]
  4. Bisaccia E., Berger C., Klainer A. S. Extracorporeal photopheresis in the treatment of AIDS-related complex: a pilot study. Ann Intern Med. 1990 Aug 15;113(4):270–275. doi: 10.7326/0003-4819-113-4-270. [DOI] [PubMed] [Google Scholar]
  5. Carpenter S., Kraus G. A. Photosensitization is required for inactivation of equine infectious anemia virus by hypericin. Photochem Photobiol. 1991 Feb;53(2):169–174. doi: 10.1111/j.1751-1097.1991.tb03919.x. [DOI] [PubMed] [Google Scholar]
  6. Clouse K. A., Powell D., Washington I., Poli G., Strebel K., Farrar W., Barstad P., Kovacs J., Fauci A. S., Folks T. M. Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone. J Immunol. 1989 Jan 15;142(2):431–438. [PubMed] [Google Scholar]
  7. Durán N., Song P. S. Hypericin and its photodynamic action. Photochem Photobiol. 1986 Jun;43(6):677–680. doi: 10.1111/j.1751-1097.1986.tb05646.x. [DOI] [PubMed] [Google Scholar]
  8. Folks T. M., Clouse K. A., Justement J., Rabson A., Duh E., Kehrl J. H., Fauci A. S. Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2365–2368. doi: 10.1073/pnas.86.7.2365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Giulivi C., Sarcansky M., Rosenfeld E., Boveris A. The photodynamic effect of rose bengal on proteins of the mitochondrial inner membrane. Photochem Photobiol. 1990 Oct;52(4):745–751. doi: 10.1111/j.1751-1097.1990.tb08676.x. [DOI] [PubMed] [Google Scholar]
  10. Harada S., Koyanagi Y., Yamamoto N. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science. 1985 Aug 9;229(4713):563–566. doi: 10.1126/science.2992081. [DOI] [PubMed] [Google Scholar]
  11. Hoxie J. A., Alpers J. D., Rackowski J. L., Huebner K., Haggarty B. S., Cedarbaum A. J., Reed J. C. Alterations in T4 (CD4) protein and mRNA synthesis in cells infected with HIV. Science. 1986 Nov 28;234(4780):1123–1127. doi: 10.1126/science.3095925. [DOI] [PubMed] [Google Scholar]
  12. Hudson J. B., Lopez-Bazzocchi I., Towers G. H. Antiviral activities of hypericin. Antiviral Res. 1991 Feb;15(2):101–112. doi: 10.1016/0166-3542(91)90028-p. [DOI] [PubMed] [Google Scholar]
  13. Kalyanaraman B., Feix J. B., Sieber F., Thomas J. P., Girotti A. W. Photodynamic action of merocyanine 540 on artificial and natural cell membranes: involvement of singlet molecular oxygen. Proc Natl Acad Sci U S A. 1987 May;84(9):2999–3003. doi: 10.1073/pnas.84.9.2999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Lavie G., Valentine F., Levin B., Mazur Y., Gallo G., Lavie D., Weiner D., Meruelo D. Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5963–5967. doi: 10.1073/pnas.86.15.5963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lenard J., Bailey C. A., Miller D. K. pH dependence of influenza A virus-induced haemolysis is determined by the haemagglutinin gene. J Gen Virol. 1982 Oct;62(Pt 2):353–355. doi: 10.1099/0022-1317-62-2-353. [DOI] [PubMed] [Google Scholar]
  17. Lenard J., Miller D. K. pH-dependent hemolysis by influenza, Semliki, Forest virus, and Sendai virus. Virology. 1981 Apr 30;110(2):479–482. doi: 10.1016/0042-6822(81)90079-9. [DOI] [PubMed] [Google Scholar]
  18. Lenard J., Vanderoef R. Localization of the membrane-associated region of vesicular stomatitis virus M protein at the N terminus, using the hydrophobic, photoreactive probe 125I-TID. J Virol. 1990 Jul;64(7):3486–3491. doi: 10.1128/jvi.64.7.3486-3491.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Meruelo D., Lavie G., Lavie D. Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5230–5234. doi: 10.1073/pnas.85.14.5230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miller D. K., Feuer B. I., Vanderoef R., Lenard J. Reconstituted G protein-lipid vesicles from vesicular stomatitis virus and their inhibition of VSV infection. J Cell Biol. 1980 Feb;84(2):421–429. doi: 10.1083/jcb.84.2.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. North J., Freeman S., Overbaugh J., Levy J., Lansman R. Photodynamic inactivation of retrovirus by benzoporphyrin derivative: a feline leukemia virus model. Transfusion. 1992 Feb;32(2):121–128. doi: 10.1046/j.1537-2995.1992.32292180139.x. [DOI] [PubMed] [Google Scholar]
  22. Roat M. I., Romanowski E., Araullo-Cruz T., Gordon Y. J. The antiviral effects of rose bengal and fluorescein. Arch Ophthalmol. 1987 Oct;105(10):1415–1417. doi: 10.1001/archopht.1987.01060100117039. [DOI] [PubMed] [Google Scholar]
  23. Schinazi R. F., Chu C. K., Babu J. R., Oswald B. J., Saalmann V., Cannon D. L., Eriksson B. F., Nasr M. Anthraquinones as a new class of antiviral agents against human immunodeficiency virus. Antiviral Res. 1990 May;13(5):265–272. doi: 10.1016/0166-3542(90)90071-e. [DOI] [PubMed] [Google Scholar]
  24. Sieber F., O'Brien J. M., Krueger G. J., Schober S. L., Burns W. H., Sharkis S. J., Sensenbrenner L. L. Antiviral activity of merocyanine 540. Photochem Photobiol. 1987 Nov;46(5):707–711. doi: 10.1111/j.1751-1097.1987.tb04836.x. [DOI] [PubMed] [Google Scholar]
  25. Tang J., Colacino J. M., Larsen S. H., Spitzer W. Virucidal activity of hypericin against enveloped and non-enveloped DNA and RNA viruses. Antiviral Res. 1990 Jun;13(6):313–325. doi: 10.1016/0166-3542(90)90015-y. [DOI] [PubMed] [Google Scholar]
  26. Turner G. S., Kaplan C. Photoinactivation of vaccinia virus with rose bengal. J Gen Virol. 1968 Dec;3(3):433–443. doi: 10.1099/0022-1317-3-3-433. [DOI] [PubMed] [Google Scholar]
  27. Valenzeno D. P. Photomodification of biological membranes with emphasis on singlet oxygen mechanisms. Photochem Photobiol. 1987 Jul;46(1):147–160. doi: 10.1111/j.1751-1097.1987.tb04749.x. [DOI] [PubMed] [Google Scholar]
  28. Valenzeno D. P., Pooler J. P. Cell membrane photomodification: relative effectiveness of halogenated fluoresceins for photohemolysis. Photochem Photobiol. 1982 Mar;35(3):343–350. doi: 10.1111/j.1751-1097.1982.tb02572.x. [DOI] [PubMed] [Google Scholar]
  29. Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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