MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
The cytokine interleukin-28B (IL-28B) has potential antiviral properties and regulatory roles in adaptive cellular immunity. A genome-wide association study identified a single nucleotide polymorphism near the IL-28B gene that strongly predicts response to hepatitis C treatment with interferon and ribavirin. In this study, we produced human serum albumin (HSA) fused to interleukin-28B (HSA-IL28B) in an attempt to determine the effects of albumin fusion on anti-Hepatitis C virus (HCV) activity and protein stability. HSA-IL28B was expressed at high levels in the yeast expression system we used and was easily purified. The biological activities of IL-28B were only retained when HSA was fused at the N-terminus. Compared with the native IL-28B, HSA-IL28B showed improved protein stability. HSA-IL28B inhibited HCV infection through the membrane receptors IL28R1and IL10R2. Additionally, we demonstrated that HSA-IL28B was able to induce interferon-stimulated genes, phosphorylate intracellular STAT1, and act in restricted cell types. Our findings highlight the potential clinical applications of the fusion protein during virus infection and for immune regulation.