Antiplatelet Drug Therapy Moderates Immune-mediated Liver Disease and Inhibits Viral Clearance in Mice Infected with a Replication-deficient Adenovirus

Treatment with a low dose of combined aspirin and clopidogrel, two antiplatelet drugs widely used in humans, markedly reduced the homing of virus-specific cytotoxic T lymphocytes and virus-nonspecific inflammatory leukocytes to the liver of mice acutely infected with a hepatotropic, replication-deficient, lacZ-expressing adenovirus (RAd35). Consequently, aspirin/clopidogrel-induced platelet dysfunction greatly diminished liver disease severity and inhibited viral clearance. Along with the finding that aspirin/clopidogrel caused neither bleeding nor anemia, our results suggest that antiplatelet drugs may be considered to limit excessive liver immunopathology and/or to facilitate the persistence of hepatotropic viral vectors utilized in gene therapy.