Unraveling the molecular mechanism governing the tissue specific expression of IFN-lamda-R1

The functional receptor for type III interferons [IFNs] is a heterodimer of IFNLR1 and IL10R2. IFNLR1 is expressed in a highly tissue specific manner, with epithelial and liver tissue as the prime expressing tissues in humans. However, knowledge about the molecular pathways responsible for regulating the expression of IFNLR1 is yet unknown. In this study, various bioinformatics tools were used to predict the scores of signal peptides of IFN-lamda-R1 and IFN-lamda-R1, which was considered as an important difference in the expression of both receptors or participation in regulating the IFNLR1 gene. In silico study revealed that the signal peptide of IFN-lamda-R1 had more potential than the signal peptide of IFN-lamda-R1 but changing the signal peptide of wild type IFN-lamda-R1 with the signal peptide of IFN-lamda-R1 in wet lab had barely shown any differences. Selective expression of IFN-lamda-R1 was considered to be a plus point towards the targeted anti-viral activity of IFN-lamda-s but artificial control on its expression will surely make IFN-lamda-s a better drug with enhanced activity. The results of this study may help us in contributing some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities involved

Over expression of a synthetic gene encoding interferon lambda using relative synonymous codon usage bias in Escherichia coli

Interferon Lambda [IFN- Lamda] is a type III interferon which belongs to a novel family of cytokines and possesses antiviral and antitumor properties. It is unique in its own class of cytokines; because of the specificity towards its heterodimer receptors and its structural similarities with cytokines of other classes. This renders IFN- Lamda a better choice for the treatment against many diseases including viral hepatitis and human coronavirus [HCoV-EMC]. The present study describes a computational approach known as relative synonymous codon usage [RSCU]; used to enhance the expression of IFN- Lamda protein in a eukaryotic expression system. Manually designed and commercially synthesized IFN- Lamda gene was cloned into pET-22b expression plasmid under the control of inducible T7-lac promoter. Maximum levels of IFN- Lamda expression was observed with 0.4 mM IPTG in transformed E. coli incubated for 4 hours in LB medium. Higher concentrations of IPTG had no or negative effect on the expression of IFN- Lamda. This synthetically over expressed IFN- Lamda can be tested as a targeted treatment option for viral hepatitis after purification