Cytomegalovirus (CMV) infection in immunocompromised patients may result in severe morbidity and mortality. The standard of care for these patients is the use of CMV-seronegative blood components. Alternatively, filtered, leukocyte-reduced blood components have been used. However, neither approach completely prevented transfusion-associated CMV infection in the recipients. The Helinx technology (Cerus Corp, Concord, CA) utilizing amotosalen hydrochloride (HCl) (S-59) and long-wavelength ultraviolet A (UVA) light, was developed to enhance the safety of platelet transfusion. The combination of 150 micromol/L of S-59 and a 3 J/cm2 UVA treatment inactivated greater than 10(5.9 +/- 0.3) plaque-forming units (pfus) per milliliter of CMV in full-sized therapeutic platelet concentrates. The efficacy margin of this treatment is greater than 100-fold. In an immunocompromised in vivo murine transfusion model, mice transfused with platelets contaminated with murine CMV (MCMV)-infected splenocytes became MCMV-positive, exhibited histologic evidence of CMV disease, and died. Mice transfused with Helinx-treated platelets contaminated with MCMV-infected splenocytes prior to treatment remained MCMV-negative with no histologic evidence of CMV disease and remained healthy. These results demonstrated that Helinx treatment of MCMV-contaminated platelet concentrates prevented MCMV infection by platelet transfusion in immunodeficient animals. In conclusion, Helinx technology offers a potential alternative to selection of CMV-seronegative units and to leukocyte-reduction filtration as a means to decrease the risk of transfusion-acquired CMV infection.