ANTIVIRAL EFFECTS OF MEROCYANINE DYES

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The transmission of pathogenic viruses such as HTLV-III/LAV by blood or blood products remains a serious health problem. Donor screening, no matter how extensive, will not be able to make the blood supply entirely safe in the foreseeable future, because mutant viruses may escape immunologic detection methods, and recently infected individuals may not yet have a detectable antibody titer at the time of the blood donation. Furthermore, shrinking pools of eligible donors will make it more and more difficult to meet the growing demand for virus-free blood products for immunosuppressed patients. This situation has renewed the interest in blood sterilization procedures. We have recently observed that simultaneous exposure to the amphipathic dye, merocyanine 540 (MC 540) and visible light rapidly inactivates several enveloped viruses (Friend erythroleukemia, herpes simplex-1, and HTLV-1) and some virus-infected cells, but apparently spares mature circulating blood cells, piuripotent hematopoietic stem cells, and at least some coagulation factors. An additional advantage of this method is that the systemic toxicity of MC 540 is very low. Based on what we know about the mechanism of MC 540-mediated photosensitization, we predict that the dye should be effective against most enveloped viruses, including cytomegalovirus (CMV) and HTLV-III. To test this hypothesis, we will 1) quantitatively determine the effects of merocyanine dyes and light on several enveloped viruses (herpes simplex-1/2, CMV, HTLV-I/III) and one non-enveloped virus (adenovirus 2) and virus-infected/transformed cells. 2) We will elucidate selected aspects of the underlying mechanisms of action, 3) determine the structural and functional integrity of photosensitized normal blood cells, marrow cells, and coagulation factors, 4) determine the antigenicity of photosensitized viruses, and 5) examine the mutagenic potential of MC 540-mediated photosenitization and the oncogenic potential of photosensitized viruses. The proposed work has implications for the preparation of virus-free blood products and vaccines, the treatment of virus- induced skin and eye lesions, and perhaps the systemic treatment of virus infections by extracorporeal photopheresis. It will also lead to new insights into the mechanism of action of polymethine photosensitizers.