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

Copyright © 2019 Elsevier Ltd. All rights reserved..

Interferon lambda 4 (IFNλ4) 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 IFNλ4 from a mammalian cell line through a glycoengineering and structure-based approach. We introduced de novo N-glycosylation of IFNλ4, guided by structural analysis, and produced IFNλ4 variants in Expi293F that displayed improved expression and potency. To preserve the structure and functionality of IFNλ4, the model structure of the IFNλ4 signaling complex was analyzed and the N-glycosylation candidate sites were selected. The receptor binding activity of engineered IFNλ4 variants and their receptor-mediated signaling pathway were similar to the E. coli version of IFNλ4 (eIFNλ4), while the antiviral activity and induction levels of interferon-stimulated gene (ISG) were all more robust in our variants. Our engineered IFNλ4 variants may be further developed for clinical applications and utilized in basic research to decipher the immunological roles of IFNλ4.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:125

Enthalten in:

Cytokine - 125(2020) vom: 01. Jan., Seite 154833

Sprache:

Englisch

Beteiligte Personen:

Chung, Jae-Hee [VerfasserIn]
Hong, Seon-Hui [VerfasserIn]
Seo, Nari [VerfasserIn]
Kim, Tae-Shin [VerfasserIn]
An, Hyun Joo [VerfasserIn]
Lee, Pedro [VerfasserIn]
Shin, Eui-Cheol [VerfasserIn]
Kim, Ho Min [VerfasserIn]

Links:

Volltext

Themen:

9008-11-1
Anti-viral activity
Glycoengineering
Homology modeling
IFNλ4
IFNL4 protein, human
Interferons
Interleukins
Journal Article
Recombinant Proteins
Research Support, Non-U.S. Gov't
Type III interferon signaling

Anmerkungen:

Date Completed 20.05.2021

Date Revised 20.05.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.cyto.2019.154833

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM30089032X