Novel Therapy for BVDV and HCV Cytopathicity

Dr. Edward Dubovi

Abstract

Bovine Viral Diarrhea Virus (BVDV) and Hepatitis C Virus (HCV) are both genetically close members of Flaviviridae family. BVDV causes severe lesions in the gastrointestinal tract and death in affected animals. HCV is a leading course for chronic liver disease, cirrhosis, and liver cancer, with 170 million people infected worldwide. There is currently no satisfactory treatment against either viral infection. The development of anti-HCV therapy has been greatly hindered by the lack of a cell or animal model. Cytopathic strain of BVDV (cpBVDV) is commonly used as a surrogate model for HCV infection, and mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in cpBVDV-induced cell death. The goal of this seed grant is to determine whether a family of novel mitoprotective and antioxidant peptides (SS peptides) can protect against cell death caused by cpBVDV. Our specific aims are:

1. To determine the ability of SS peptides to reduce cpBVDV cytopathicity in cell cultures.

2. To determine the contribution of necrosis versus apoptosis in cyBVDV cytopathicity, and to determine the efficacy of SS peptides against the two types of cell death.

3. To determine the role of mitochondrial dysfunction versus ROS in mediating BVDV-induced apoptosis.