Selective antiviral activity of synthetic soluble L-tyrosine and L-dopa melanins against human immunodeficiency virus in vitro.
Melanins are pigments found in hair, skin, irides of the eye, and brain. Their functions in mammals include protection from exposure to sunlight, camouflage from predators, sexual recognition within species, and possible electron transfer reactants. Most natural melanins exist in an insoluble form, which is one reason there is little information on the biological properties of soluble melanins. Here, synthetic soluble melanins were obtained by chemical oxidation of L-tyrosine or spontaneous oxidation of L-beta-3,4-dihydroxyphenylalanine (L-dopa). Replication of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) was inhibited by soluble melanin in two human lymphoblastoid cell lines (MT-2 and H9) and in phytohemagglutinin-stimulated human T cells. Effective concentrations of 0.15-10 micrograms/ml had no cell toxicity. Melanin blocked infection by cell-free virus and interfered with HIV-induced syncytium formation and cytopathic effects when fusion-susceptible, uninfected cells, were mixed with chronically infected cells. Melanin also impeded the HIV-1 envelope surface glycoprotein, and T cell specific monoclonal antibody leu-3a (CD4), but not leu-5b (CD2), from binding to the surface of MT-2 cells. No effect on HIV-1 reverse transcriptase activity in viral lysates was observed. These results identify a unique biological property of melanin, and suggest that soluble melanins may represent a new class of pharmacologically active substances which should be further investigated for potential therapeutic utility in the treatment of Acquired Immune Deficiency Syndrome (AIDS).
Montefiori
D C
DC
Department of Pathology, Vanderbilt University Medical School, Nashville, Tennessee 37232.
Zhou
J Y
JY
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015686:Gene Products, env / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D015498:HIV-2 / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D006801:Humans; D010835:Phytohemagglutinins / Q000494:pharmacology; D011498:Protein Precursors / Q000276:immunology; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D014443:Tyrosine / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D018801:CD2 Antigens; D015704:CD4 Antigens; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D010835:Phytohemagglutinins; D011498:Protein Precursors; D011971:Receptors, Immunologic; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; C040616:DOPA melanin; D012194:RNA-Directed DNA Polymerase