Protein Eng Des Sel. 2018 Nov 29. doi: 10.1093/protein/gzy029. [Epub ahead of print]
The generation and biological activity of a long-lasting recombinant human interferon-λ1.
Yuan WM1,2, Zhang R3, Zhang Q2, Ma FL2, Wang C2, Wang YZ3, Zeng Y1, Zheng LS2.
Author information
1
Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Department of Biochemistry, School of Medicine, Shihezi University, Shihezi, Xinjiang, China.
2
Key Laboratory for Medical Virology, National Health Commission, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
3
Medical Teaching Experiment Center, School of Medicine, Shihezi University, Shihezi, Xinjiang, China.
Abstract
The previously generated recombinant human (rh) interferon (IFN)-λ1 protein has a short half-life, and this feature makes it challenging to conduct studies on potential clinical applications for rhIFN-λ1. In an attempt to overcome this difficulty, we constructed a 'long-life' version of rhIFN-λ1. This modified rhIFN-λ1, named rhIFN-λ1-CTPON, has a human chorionic gonadotropin β subunit carboxyl-terminal peptide (CTP) and an N-glycosylation sequence linked to its C-terminus. We confirmed the sequence of rhIFN-λ1-CTPON by mass spectrometry and then measured its biological activities. The results show that rhIFN-λ1-CTPON had antiviral activity and anti-proliferation activity in vitrothat were similar to those of rhIFN-λ1 and that it similarly promoted natural killer cell cytotoxicity. Notably, the in vivo half-life of rhIFN-λ1-CTPON was determined to be 3-fold higher than that of rhIFN-λ1. We also assessed the anti-hepatitis B virus activity of rhIFN-λ1-CTPON; it was able to inhibit the production of the antigens HBs-Ag and HBe-Ag and induce antiviral gene expression. In conclusion, rhIFN-λ1-CTPON has a longer half-life than rhIFN-λ1 and has similar biological activities, so rhIFN-λ1-CTPON is an appropriate substitute for rhIFN-λ1 in the further study of potential clinical applications for rhIFN- λ1.
PMID:
30496575
DOI:
10.1093/protein/gzy029
作者: StephenW 时间: 2018-12-1 06:06
Protein Eng Des Sel。 2018年11月29日doi：10.1093 / protein / gzy029。 [提前打印]
长效重组人干扰素-λ1的产生和生物活性。
元WM1,2，张R3，张Q2，马FL2，王C2，王YZ3，曾Y1，郑LS2。
作者信息