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

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Interferon lambda 4 (IFN lambda 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 lambda 4 from a mammalian cell line through a glycoengineering and structure-based approach. We introduced de novo N-glycosylation of IFN lambda 4, guided by structural analysis, and produced IFN lambda 4 variants in Expi293F that displayed improved expression and potency. To preserve the structure and functionality of IFN lambda 4, the model structure of the IFN lambda 4 signaling complex was analyzed and the N-glycosylation candidate sites were selected. The receptor binding activity of engineered IFN lambda 4 variants and their receptor-mediated signaling pathway were similar to the E. coli version of IFNM (eIFN lambda 4), while the antiviral activity and induction levels of interferon-stimulated gene (ISG) were all more robust in our variants. Our engineered IFN lambda 4 variants may be further developed for clinical applications and utilized in basic research to decipher the immunological roles of IFN lambda 4.
Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Issue Date
2020-01
Language
English
Article Type
Article
Citation

CYTOKINE, v.125

ISSN
1043-4666
DOI
10.1016/j.cyto.2019.154833
URI
http://hdl.handle.net/10203/270726
Appears in Collection
MSE-Journal Papers(저널논문)
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