title: Strategies for evaluation of enveloped virus inactivation in red cell concentrates using hypericin.
abstract: 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 key enveloped viruses in packed red cell concentrates (PRC) was evaluated. In addition to inactivating effectively > or = 10(6) TCID50 of human immunodeficiency virus (HIV), inactivation of bovine viral diarrhea virus (BVDV) in PRC was used as a model for hepatitis C virus to overcome the deficiency in reliable experimental systems for hepatitis C virus (HCV) inactivation. BVDV was two orders of magnitude more sensitive to inactivation by hypericin than HIV. As part of the virucidal efficacy analyses, the effects of photosensitization on hemopoietic cell lines carrying quiescent integrated HIV provirus were studied as models for evaluating virus inactivation in latently infected cells. Phorbol ester-induced virus production by these cells was effectively prevented by photosensitization with hypericin. A refinement of the illumination conditions, incorporating a monochromatic sodium light source with an emission spectrum coinciding with the absorption peak of hypericin, was highly virucidal, however, caused unacceptable levels of hemolysis. Red blood cells could be protected from phototoxic cellular damage by complexing hypericin with human serum albumin (albumin-hypericin), but the decrease in hemolysis was at the expense of virucidal efficacy. Thus, excitation of hypericin with a fluorescent source appears to be useful potentially for virus inactivation in PRC.
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center 10021, USA. aprince@nybc.org
authors.forename: A M
authors.initials: AM
authors.lastname: Prince
authors.forename: D
authors.initials: D
authors.lastname: Pascual
authors.forename: D
authors.initials: D
authors.lastname: Meruelo
authors.forename: L
authors.initials: L
authors.lastname: Liebes
authors.forename: Y
authors.initials: Y
authors.lastname: Mazur
authors.forename: E
authors.initials: E
authors.lastname: Dubovi
authors.forename: M
authors.initials: M
authors.lastname: Mandel
authors.forename: G
authors.initials: G
authors.lastname: Lavie
mesh_terms: D000818:Animals; D000873:Anthracenes; D019380:Anti-HIV Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002417:Cattle; D002474:Cell-Free System; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000528:radiation effects; D004912:Erythrocytes / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008027:Light; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin