Abstract
BackgroundAs a key link between innate and adaptive immune responses, the interferon (IFN) system is the first line of defense against viral infection. IFN, and in particular, IFN-α, has been used clinically as an effective therapeutic agent for viral infections. However, different subtypes of IFN-α demonstrate distinct antiviral activity. Therefore, it is important to identify IFN-α subtypes with high antiviral activity for the development of genetically engineered antiviral drugs.ResultsIn this study, we cloned the genes for 13 IFN-α subtypes from peripheral blood lymphocytes of the mink. The homologies of the 13 mink IFN-α genes were 93.6–99.3% and 88.8–98.4% at the nucleotide and amino acid sequence levels, respectively. In contrast to human and canine IFN-α subtypes, most mink IFN-α subtypes contained two N-glycosylation sites. We expressed and purified 13 mink IFN-α subtypes in Escherichia coli. The cytopathic effect inhibition assay showed that all the 13 recombinant mink IFN-α subtypes inhibited the propagation of vesicular stomatitis virus in WISH cells, with IFN-α2 and IFN-α12 demonstrating the highest activities. Furthermore, recombinant mink IFN-α2 and IFN-α12 significantly suppressed the propagation of canine distemper virus in Vero cells, with IFN-α2 demonstrating the highest activity.ConclusionsWe identified the mink IFN-α2 subtype as a promising candidate for the development of effective antiviral drugs.
Highlights
As a key link between innate and adaptive immune responses, the interferon (IFN) system is the first line of defense against viral infection
The type III interferons are known as the IFN-λs and are more related to type I IFNs based on their amino acid sequence and protein function
DNAStar software analysis demonstrated that the cDNAs of 13 subtypes of mink IFN-α (MiIFN-α) were 564 bp long and encoded 187 amino acids
Summary
As a key link between innate and adaptive immune responses, the interferon (IFN) system is the first line of defense against viral infection. IFN belongs to the cytokine family of proteins and has a wide range of physiological functions, such as inhibiting viral infection, regulating cell proliferation and differentiation, and modulating immune responses [2]. The type III interferons are known as the IFN-λs and are more related to type I IFNs based on their amino acid sequence and protein function. The more limited tissue expression of IFN-λ receptors suggests that type III IFNs do not recapitulate the type I IFN antiviral system. They have antiviral effects in the respiratory tract, gastrointestinal tract, skin mucosa, epithelial cells, and some tumor cells.
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