| 其他摘要 | Interferons (IFNs) are key cytokines in the establishment of a multi-faceted antiviral response. Three distinct types of IFNs are now recognized (type I, II and III) based on their structural features, receptor usage and biological activities. As tree shrews (Tupaia belangeri) have shown susceptibility to several human viruses, they are a potentially important model for analyzing viral infection. However, little is known about their IFNs system. We used the tree shrew genome to retrieve type I and type III IFNs and their receptor contig sequences by BLASTN and BLASTZ algorithms, and GenScan was used to scan transcripts from the putative contig sequences. RT-PCR and bioinformatic methods were then used to clone and characterize the IFNs system. Our data show that tree shrew interferon system includes: type I IFN: α (five subtypes), β, ω, κ, ε, δ; type II IFN: γ; type III IFN: λ3. Furthermore, the predicted structures of α and λ have similar character with those of other mammals. However, there are some differences in cysteine position and N-glycosylation numbers between human and tree shrew IFNs. Due to the highest identity with human IFN-λ3, we opted to define one intact IFN-λ gene, tsIFN-λ3, as well as its two receptor subunits, tsIFNλR1 and tsIL10R2. Additionally, our results showed that tsIFN-λ3 contained many features conserved in IFN-λ3 genes from other mammals, including conserved signal peptide cleavage and glycosylation sites, and several residues responsible for binding to the type III IFNR. We also found six transcript variants in the receptors: three in tsIFNλR1, wherein different extracellular regions exist in three transmembrane proteins, resulting in different affinities with IFN-λ; and three more variants in tsIL10R2, encoding one transmembrane and two soluble proteins. Based on tissue distribution in the liver, heart, brain, lung, intestine, kidney, spleen, and stomach, we found that IFN-λ receptor complex was expressed in a variety of organs although the expression level differed markedly between them. As the first study to identify all IFNs of tree shrews and transcript variants in IL-10R2, our study offers novel insights that may have important implications for the role of IFN s in tree shrews’ susceptibility with a variety of human viruses, bolstering the arguments for using tree shrews as an animal model in the study of human viral infections. |
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