Expressionof Unmodified Hepatitis C Virus Envelope Glycoprotein-Coding SequencesLeads to Cryptic Intron Excision and Cell Surface Expression of E1/E2Heterodimers Comprising Full-Length and Partially DeletedE1

Hepatitis C virus (HCV) is a positive-strand RNA virus that replicates exclusively in the cytoplasm of infected cells. The viral envelope glycoproteins, E1 and E2, appear to be retained in the endoplasmic reticulum, where viral budding is thought to occur. Surprisingly, we found that the expression system used to generate HCV envelope glycoproteins influences their subcellular localization and processing. These findings have important implications for optimizing novel HCV fusion and entry assays as well as for budding and virus particle formation.