Document 0033
 DOCN  M9480033
 TI    Differential sensitivities of viruses in red cell suspensions to
       methylene blue photosensitization.
 DT    9410
 AU    Wagner SJ; Robinette D; Storry J; Chen XY; Shumaker J; Benade L; Product
       Development Department, Jerome H. Holland Laboratory,; American Red
       Cross Blood Services, Rockville, Maryland.
 SO    Transfusion. 1994 Jun;34(6):521-6. Unique Identifier : AIDSLINE
       MED/94295069
 AB    BACKGROUND: Previous studies explored the feasibility of using the
       photosensitizer methylene blue (MB) as a virucidal agent in red cell
       suspensions. Under treatment conditions (5 microM [5 mumol/L] MB, 3.4 x
       10(4) J/m2) that resulted in more than 6 log10 inactivation of vesicular
       stomatitis virus (VSV) or of the enveloped bacteriophage phi 6, red cell
       membrane alterations were observed. Increased red cell ion permeability
       and the binding of plasma proteins to the red cell surface were the most
       sensitive indicators, which varied in a dose-dependent fashion. STUDY
       DESIGN AND METHODS: Inactivation of three additional extracellular
       viruses and intracellular human immunodeficiency virus type 1 (HIV-1)
       was assessed after MB phototreatment of red cell suspensions. Potassium
       leakage and IgG binding also were characterized in MB-treated red cell
       suspensions that were exposed to low-fluence light (6 x 10(3) J/m2).
       RESULTS: Different viruses exhibit a wide range of sensitivities to MB
       photoinactivation. For example, phototreatment conditions (5 microM [5
       mumol/L] MB, 3.4 x 10(4) J/m2) that inactivated more than 6 log10 of VSV
       did not inactivate the nonenveloped picornavirus, encephalomyocarditis
       virus. In contrast, lower fluences (6 x 10(3) J/m2) inactivated
       approximately 5 log10 or more of Sindbis virus and approximately 4log10
       of extracellular HIV-1. These less stringent phototreatment conditions
       (5 microM [5 mumol/L] 6 x 10(3) J/m2) caused lower rates of red cell
       potassium leakage (reduction by 6-fold) and little or no binding of
       plasma proteins to the red cell surface, compared to values observed
       previously with higher fluences. However, neither 6 x 10(3) nor 4.1 x
       10(4) J per m2 fluences resulted in any inactivation of intracellular
       HIV as represented by changes in the amount of p24 antigen produced
       during co-culture of actively infected H9 cells. CONCLUSION: MB-based
       protocols would require the use of high-efficiency (> 6log10) white
       cell-reduction filters or additional inactivation steps to deplete or
       inactivate intracellular virus.
 DE    Encephalomyocarditis Virus/DRUG EFFECTS  Erythrocytes/*MICROBIOLOGY
       Hepatitis C Viruses/DRUG EFFECTS  Human  HIV-1/*DRUG EFFECTS  IgG/BLOOD
       Kinetics  Light  Methylene Blue/*PHARMACOLOGY  Photosensitizing
       Agents/*PHARMACOLOGY  Potassium/BLOOD  Sindbis Virus/DRUG EFFECTS
       Support, Non-U.S. Gov't  Viruses/*DRUG EFFECTS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).