Preactivated merocyanine 540 inactivates HIV-1 and SIV: potential therapeutic and blood banking applications.
A novel photodynamic procedure employing "preactivated" merocyanine 540 (P-MC 540) was assessed for its effectiveness in inactivating human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Merocyanine 540 was preactivated by exposure to laser light at 514 nm prior to addition to viruses or infected cells. Treatment of cell-free HIV-1 and SIV with P-MC 540 significantly reduced their ability to infect and kill MT-4 cells in vitro. Preactivated MC 540 treatment of in vitro HIV-1-infected human peripheral blood mononuclear cells also decreased viral infection as assessed by a reduction in the amounts of HIV-1 p24 antigen produced and in the number of HIV-1 antigen-positive cells. Indirect immunofluorescence assays of target cell binding showed that treatment of cell-free HIV-1 and SIV with P-MC 540 interfered with their ability to bind to CD4+ target cells. Immunoprecipitation with a monoclonal anti-CD4 antibody of P-MC 540-treated and radiolabeled HIV-1 incubated with soluble recombinant CD4 (srCD4) resulted in coprecipitation of HIV-1 viral p17 and p24 core antigens with the envelope gp120/CD4 complex, suggesting cross-linking of viral components. However, no significant decrease in the binding of treated HIV-1 to srCD4 was observed. Because of the antitumor and antiviral properties of P-MC 540, this photopreactivation procedure may represent a promising therapeutic means for controlling systemic malignancies and viral infections, and for eliminating viral contaminants in biological fluids. Unlike conventional phototherapy, this procedure does not require the delivery of light energy at the target sites following binding of the photosensitizing compounds.
Tran
C C
CC
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228-0147.
Allan
J S
JS
Pervaiz
S
S
Matthews
J L
JL
Trevino
S R
SR
Gulliya
K S
KS
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001771:Blood Banks; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008027:Light; D011744:Pyrimidinones / Q000494:pharmacology* / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000254:growth & development
D000998:Antiviral Agents; D015704:CD4 Antigens; D011744:Pyrimidinones; D011838:Radiation-Sensitizing Agents; C003954:merocyanine dye