Investigation On Inhibition Effects Of Photodynamic Therapy On Human Immunodeficiency Virus Infection

Acquired immunodeficiency syndrome (AIDS) has spread worldwide currently, which is threatening human health and the development of world economics seriously. Photodynamic therapy (PDT) is a new method in laser medcine. In the 1990s, the study of photoinactivation of human immunodeficiency virus(HIV) in blood products was a focus of intense investigation but the side effects of photosensitizers and technical issues with lasers hampered research. Since these initial studies, a series of new photosensitizers have been developed and new laser technologies have emerged, making the prospect of treating AIDS by PDT more promising. The current study explored the potential of in vitro photoinactivation of HIV by PDT with a new photosensitizer, hematoporphyrin monomethyl ether (HMME).Objective:Through exploring the potential and mechanism of anti-HIV activities based on HMME-PDT, analysising the relationships between the anti-HIV effects of PDT and photosensitizers concentration, power density, energy density and antioxidants, evaluating the preclinical pharmacodynamic effects of PDT anti-HIV, we expected these studies could provide academic and experimental evidence for the treatment of AIDS using PDT in clinic.Methods:1. The protection assay in acute infected MT-4 was assessed by MTT method, reduction of p24 antigen expression level in chronically infected H9 was measured by ELISA, the inhibition of cell-cell and virus-cell fusion induced by HIV-1â…¢B were observed and the activities to inactivate HIV-1â…¢B free particles were detected by ELISA.2. The anti-HIV effects of PDT with different doses of photosensitizers, power density, and energy density, and in present of two antioxidants including sodium azide and D-mannitol were accessed by ELISA to explore the influential factors of PDT anti-HIV. 3. The activities to inhibit the infectivity of HIV free particles including HIV-1â…¢BA17,HIV-1 L10R/M46I/L63P/V82T/I84V,HIV-1 Protease Gene Mutants RF/V82F/184V,pNL4-3 gp41 (36G) N42S,pNL4-3 gp41 (36G) V38A, N42T,HIV-1KM018,HIV-1SF162,HIV-2CBL20 and HIV-2ROD were measured by ELISA to evaluate the preclinical pharmacodynamic effects of PDT anti-HIV.Results:1. HMME-PDT inhibited the cell-cell membrane fusion up to 64.68%(P<0.05) and virus-cell fusion up to 85%(P<0.05) significantly. Cell-free virus inhibition of up to 100%(P<0.05) was achieved by each treatment. However, PDT had little effect on the acute infection or chronic infection of HIV-1â…¢B.2. Within a certain range, the inhibition rates of cell-free HIV-1â…¢B were typically increased in proportion to the augment of HMME concentration and energy density, but in inverse proportion to power density. Both sodium azide and D-mannitol could weaken the anti-HIV-cell fusion activities of PDT, and the latter done better (P<0.05).3. The infectivity of cell-free virus HIV-1â…¢BA17,HIV-1 L10R/M46I/L63P/V82T/I84V,HIV-1 Protease Gene Mutants RF/V82F/184V,pNL4-3 gp41 (36G)N42S,pNL4-3 gp41 (36G) V38A, N42T,HIV-1KM018,HIV-1SF162,HIV-2CBL20 and HIV-2ROD were all been inhibited significantly by HMME-PDT, with the inhibition rate up to 100%(P<0.05).Conclusion:HMME-PDT could inhibit the activity of HIV-induced membrane fusion and the infectivity of cell-free HIV. The anti-HIV effects of HMME-PDT are associated with HMME concentration, energy density, power density and antioxidant. These results suggest that PDT may be a promising new treatment for HIV infected individuals, especially those with high viral load.