Assessing hepatitis B virus infectivity in blood components following pathogen reduction using a human hepatocyte...

Area of Science:

• Blood safety research
• Virology
• Hepatology

Background:

• Pathogen reduction technologies (PRTs) are crucial for mitigating transfusion-transmitted infections.
• Evaluating PRT efficacy against hepatitis B virus (HBV) is challenging due to limited robust model systems.
• Surrogate viruses may not accurately reflect human HBV susceptibility to PRTs.

Purpose of the Study:

• To develop and validate a novel model system for assessing PRT activity against authentic human HBV.
• To evaluate the efficacy of the nucleic acid crosslinking compound S-303 against HBV in whole blood.

Main Methods:

• Whole blood spiked with HBV-positive plasma was treated with S-303 or left untreated.
• Treated and untreated blood components were used to inoculate human hepatocyte cultures from chimeric mice.
• Hepatocyte cultures were monitored for hepatitis B surface antigen (HBsAg), viral DNA, and covalently closed circular DNA (cccDNA) formation.

Main Results:

• The developed culture system accurately measured infectious HBV in blood components.
• S-303 treatment at low concentrations (0.125 mM) and short incubation times (1 hour) prevented HBV infection.
• S-303 inhibited the accumulation of HBV DNA resistant to T5 exonuclease, indicating prevention of cccDNA establishment.

Conclusions:

• A new model using humanized mouse hepatocytes and donor-derived HBV effectively evaluates PRT efficacy.
• S-303 demonstrates potent inactivation of authentic human HBV in whole blood.
• This model facilitates the assessment of PRTs against transfusion-transmitted HBV.