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ANTIVIRAL EFFECTS OF MEROCYANINE DYES

部花青染料的抗病毒作用

基本信息

批准号：
3138191
负责人：
Fritz Sieber
金额：
$ 9.86万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-09-30 至 1990-08-31
项目状态：
已结题

项目摘要

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.

病原性病毒如HTLV-III/LAV通过血液或血液制品仍然是严重的健康问题。捐助筛选，无论多么广泛，将无法使在可预见的未来，血液供应完全安全，因为突变病毒可能逃脱免疫检测方法，最近感染的人可能还没有检测到献血时的抗体滴度。此外，委员会认为，合格捐赠者的数量不断减少，难以满足日益增长的无病毒血液需求免疫抑制患者的产品。这种情况重新引起了人们对血液消毒程序的兴趣。我们有最近观察到，同时暴露于两亲性物质，染料，mercury 540（MC 540）和可见光快速灭活几种包膜病毒（Friend红白血病，单纯疱疹病毒-1和HTLV-1）和一些病毒感染的细胞，但显然不需要成熟的循环血细胞，多能的造血干细胞和至少一些凝血因子。这种方法的另一个优点是， MC 540的毒性非常低。根据我们对 MC 540介导的光敏化机制，我们预测该染料应该对大多数包膜病毒有效，包括巨细胞病毒（CMV）和HTLV-III。为了验证这一假设，我们将1）定量确定的影响 mercury染料和光对几种包膜病毒（疱疹单纯1/2、CMV、HTLV-I/III）和一种无包膜病毒（腺病毒2）和病毒感染/转化的细胞。 2)我们将阐明的基本机制的选定方面， 3）确定结构和功能的完整性光敏正常血细胞、骨髓细胞和凝血因素，4）确定光敏病毒的抗原性，和5）检查MC 540介导的致突变潜力光敏化和光敏的致癌潜力病毒拟议的工作对编写无病毒血液制品和疫苗，病毒的治疗- 引起皮肤和眼睛损伤，也许全身治疗通过体外循环血液置换术治疗病毒感染。它还将导致对聚甲炔作用机制的新见解光敏剂