Strategies for evaluation of enveloped virus inactivation in red cell concentrates using hypericin

Photodynamically induced virus inactivation appears promising in preventing transmission of enveloped virus infections in transfusible blood products. The potential for utilizing hypericin as a photosensitizer to inactivate k ey enveloped viruses in packed red cell concentrates (PRC) was evaluated. I n addition to inactivating effectively greater than or equal to 10(6) TCID5 0 of human immunodeficiency virus (HPV), inactivation of bovine viral diarr hea virus (BVDV) in PRC was used as a model for hepatitis C virus to overco me the deficiency in reliable experimental systems for hepatitis C virus (H CV) inactivation. BVDV was two orders of magnitude more sensitive to inacti vation by hypericin than HIV. As part of the virucidal efficacy analyses, t he effects of photosensitization on hemopoietic cell lines carrying quiesce nt integrated HIV provirus were studied as models for evaluating virus inac tivation in latently infected cells. Phorbol ester-induced virus production by these cells was effectively prevented by photosensitization with hyperi cin, A refinement of the illumination conditions, incorporating a monochrom atic sodium Light source with an emission spectrum coinciding with the abso rption peak of hypericin, was highly virucidal, however, caused unacceptabl e levels of hemolysis, Red blood cells could be protected from phototoxic c ellular damage by complexing hypericin with human serum albumin (albumin-hy pericin), but the decrease in hemolysis was at the expense of virucidal eff icacy. Thus, excitation of hypericin with a fluorescent source appears to b e useful potentially for virus inactivation in PRC.