Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency.

ABSTRACT: Interferon lambda 4 (IFN?4) has been recently known and studied for its role in hepatitis C virus (HCV) infection, but its clinical potential is significantly hampered due to its poor expression in vitro. Our study reports the successful production of IFN?4 from a mammalian cell line through a glycoengineering and structure-based approach. We introduced de novo N-glycosylation of IFN?4, guided by structural analysis, and produced IFN?4 variants in Expi293F that displayed improved expression and potency. To preserve the structure and functionality of IFN?4, the model structure of the IFN?4 signaling complex was analyzed and the N-glycosylation candidate sites were selected. The receptor binding activity of engineered IFN?4 variants and their receptor-mediated signaling pathway were similar to the E. coli version of IFN?4 (eIFN?4), while the antiviral activity and induction levels of interferon-stimulated gene (ISG) were all more robust in our variants. Our engineered IFN?4 variants may be further developed for clinical applications and utilized in basic research to decipher the immunological roles of IFN?4.

SUBMITTER: Chung JH 

PROVIDER: S-EPMC7129780 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature