Quantification of viral inactivation by photochemical treatment with amotosalen and UV A light, using a novel polymerase chain reaction inhibition method with preamplification

J Infect Dis. 2006 Dec 15;194(12):1737-44. doi: 10.1086/509260. Epub 2006 Nov 8.

Abstract

Background: In evaluating a photochemical treatment process for inactivating parvovirus B19, there lacked simple culture methods to measure infectivity. The recently developed enzyme-linked immunospot (ELISpot) infectivity assay uses late-stage erythropoietic progenitor cells and is labor intensive and time consuming. We evaluated a novel, efficient polymerase chain reaction (PCR) inhibition assay and examined correlations with reductions in infectivity.

Methods: Contaminated plasma was treated with 150 micromol/L amotosalen and 3 J/cm(2) ultraviolet A light and then tested for DNA modification using conventional PCR inhibition and a novel preamplification approach. The novel assay subjected the samples to preamplification cycles using long-template PCR, followed by quantitative PCR (QPCR) inhibition detection. Both approaches were tested for correlations with reductions in viral infectivity by comparing ELISpot assay results of identical samples.

Results: The B19 preamplification inhibition assay showed detection ranges of 2-2.5 log and demonstrated quantitative correlation with up to a 5.8-log reduction in viral infectivity in ELISpot results. Conventional PCR detected a >5 log reduction in amplification, correlated with a 4.4-log reduction in viral infectivity. A range of 4-log inhibition of hepatitis B virus DNA amplification was also achieved.

Conclusions: The results demonstrated that a novel preamplification QPCR assay is a useful tool for predicting reductions in infectivity after photochemical treatment. This assay was extended to show utility in circumstances where practical in vitro assays are unavailable for the determination of the efficacy of pathogen inactivation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA, Viral / genetics
  • Furocoumarins / pharmacology
  • Humans
  • Nucleic Acid Amplification Techniques
  • Parvoviridae Infections / blood
  • Parvoviridae Infections / virology
  • Parvovirus B19, Human / drug effects*
  • Parvovirus B19, Human / physiology
  • Parvovirus B19, Human / radiation effects*
  • Polymerase Chain Reaction / methods*
  • Templates, Genetic
  • Ultraviolet Rays*
  • Virus Inactivation / drug effects
  • Virus Inactivation / radiation effects

Substances

  • DNA, Viral
  • Furocoumarins
  • amotosalen