Psoralen-mediated virus photoinactivation in platelet concentrates: enhanced specificity of virus kill in the absence of shorter UVA wavelengths.
Treatments with psoralens and long-wavelength ultraviolet radiation (UVA, 320-400 nm; PUVA) have shown efficacy for virus sterilization of platelet concentrates (PC). Our laboratory has employed the psoralen derivative 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), and we have found that platelet integrity is best preserved when rutin, a flavonoid that quenches multiple reactive oxygen species, is present during AMT/UVA treatment of PC. In this report, we examine the effects of different UVA spectra under our standard PC treatment conditions (i.e. 50 micrograms/mL AMT, 0.35 mM rutin and 38 J/cm2 UVA). Added vesicular stomatitis virus (VSV; > or = 5.5 log10) was completely inactivated with the simultaneous maintenance of the platelet aggregation response (> 90% of control) when a UVA light source with transmission mainly between 360 and 370 nm (narrow UVA1) was used. In contrast, with a broad-band UVA (320-400 nm; broad UVA) light source, the aggregation response was greatly compromised (< 50% of control) with only a minor increase in the rate of VSV kill. With this lamp, platelet function could be improved to about 75% of the control by adding a long-pass filter, which reduced the transmission of shorter (< or = 345 nm) UVA wavelengths (340-400 nm; UVA1). At equivalent levels of virus kill, aggregation function was always best preserved when narrow UVA1 was used for PUVA treatment. Even in the absence of AMT, and with or without rutin present, narrow UVA1 irradiation was better tolerated by platelets than was broad UVA.(ABSTRACT TRUNCATED AT 250 WORDS)
Margolis-Nunno
H
H
New York Blood Center, NY 10021, USA.
Robinson
R
R
Horowitz
B
B
Geacintov
N E
NE
Ben-Hur
E
E
D001792:Blood Platelets / Q000187:drug effects / Q000528:radiation effects / Q000821:virology*; D005069:Evaluation Studies as Topic; D006801:Humans; D066298:In Vitro Techniques; D011701:PUVA Therapy / Q000379:methods*; D017319:Photosensitizing Agents; D014307:Trioxsalen / Q000031:analogs & derivatives; D014466:Ultraviolet Rays; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000528:radiation effects
D017319:Photosensitizing Agents; C018822:aminomethyltrioxsalen; D014307:Trioxsalen