Abstract

Risk of transmission of hepatitis C virus (HCV) by clinical plasma remains high in countries with a high prevalence of hepatitis C, justifying the implementation of viral inactivation treatments. In this study, we assessed the extent of inactivation of HCV during minipool solvent/ detergent (SD; 1% TnBP / 1% Triton X-45) treatment of human plasma. Luciferase-tagged infectious cell culture-derived HCV (HCVcc) particles were used to spike human plasma prior to treatment by SD at 31 ± 0.5° C for 30 min. Samples were taken before and after SD treatment and filtered on a Sep-Pak Plus C18 cartridge to remove the SD agents. Risk of cytotoxicity was assessed by XTT cell viability assay. Viral infectivity was analyzed based on the luciferase signals, 50% tissue culture infectious dose viral titer, and immunofluorescence staining for HCV NS5A protein. Total protein, cholesterol, and triglyceride contents were determined before and after SD treatment and C18 cartridge filtration. Binding analysis, using patient-derived HCV clinical isolates, was also examined to validate the efficacy of the inactivation by SD. SD treatment effectively inactivated HCVcc within 30 min, as demonstrated by the baseline level of reporter signals, total loss of viral infectivity, and absence of viral protein NS5A. SD specifically targeted HCV particles to render them inactive, with essentially no effect on plasma protein content and hemostatic function. More importantly, the efficacy of the SD inactivation method was confirmed against various genotypes of pa-tient-derived HCV clinical isolates and against HCVcc infection of primary human hepatocytes. Therefore, treatment by 1% TnBP / 1% Triton X-45 at 31° C is highly efficient to inactivate HCV in plasma for transfusion, showing its capacity to enhance the safety of therapeutic plasma products. We propose that the methodology used here to study HCV infectivity can be valuable in the validation of viral inactivation and removal processes of human plasma-derived products. Copyright

Original languageEnglish
Article numbere0117800
JournalPLoS One
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 6 2015

Fingerprint

Hepatitis C virus
Octoxynol
Viruses
Hepacivirus
Plasmas
inactivation
Plasma (human)
Virus Inactivation
Therapeutics
pathogenicity
luciferase
Luciferases
virion
Virion
hepatitis C
octoxynol
Tissue culture
viral proteins
Viral Proteins
Hemostatics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tnbp/triton X-45 treatment of plasma for transfusion efficiently inactivates hepatitis C virus. / Chou, Ming Li; Burnouf, Thierry; Chang, Shun Pang; Hung, Ting Chun; Lin, Chun Ching; Richardson, Christopher D.; Lin, Liang Tzung.

In: PLoS One, Vol. 10, No. 2, e0117800, 06.02.2015.

Research output: Contribution to journalArticle

Chou, Ming Li ; Burnouf, Thierry ; Chang, Shun Pang ; Hung, Ting Chun ; Lin, Chun Ching ; Richardson, Christopher D. ; Lin, Liang Tzung. / Tnbp/triton X-45 treatment of plasma for transfusion efficiently inactivates hepatitis C virus. In: PLoS One. 2015 ; Vol. 10, No. 2.
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abstract = "Risk of transmission of hepatitis C virus (HCV) by clinical plasma remains high in countries with a high prevalence of hepatitis C, justifying the implementation of viral inactivation treatments. In this study, we assessed the extent of inactivation of HCV during minipool solvent/ detergent (SD; 1{\%} TnBP / 1{\%} Triton X-45) treatment of human plasma. Luciferase-tagged infectious cell culture-derived HCV (HCVcc) particles were used to spike human plasma prior to treatment by SD at 31 ± 0.5° C for 30 min. Samples were taken before and after SD treatment and filtered on a Sep-Pak Plus C18 cartridge to remove the SD agents. Risk of cytotoxicity was assessed by XTT cell viability assay. Viral infectivity was analyzed based on the luciferase signals, 50{\%} tissue culture infectious dose viral titer, and immunofluorescence staining for HCV NS5A protein. Total protein, cholesterol, and triglyceride contents were determined before and after SD treatment and C18 cartridge filtration. Binding analysis, using patient-derived HCV clinical isolates, was also examined to validate the efficacy of the inactivation by SD. SD treatment effectively inactivated HCVcc within 30 min, as demonstrated by the baseline level of reporter signals, total loss of viral infectivity, and absence of viral protein NS5A. SD specifically targeted HCV particles to render them inactive, with essentially no effect on plasma protein content and hemostatic function. More importantly, the efficacy of the SD inactivation method was confirmed against various genotypes of pa-tient-derived HCV clinical isolates and against HCVcc infection of primary human hepatocytes. Therefore, treatment by 1{\%} TnBP / 1{\%} Triton X-45 at 31° C is highly efficient to inactivate HCV in plasma for transfusion, showing its capacity to enhance the safety of therapeutic plasma products. We propose that the methodology used here to study HCV infectivity can be valuable in the validation of viral inactivation and removal processes of human plasma-derived products. Copyright",
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