Cloning, expression and antiviral activity of mink alpha-interferons

Background: As 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-alpha, has been used clinically as an effective therapeutic agent for viral infections. However, different subtypes of IFN-alpha demonstrate distinct antiviral activity. Therefore, it is important to identify IFN-alpha subtypes with high antiviral activity for the development of genetically engineered antiviral drugs. Results: In this study, we cloned the genes for 13 IFN-alpha subtypes from peripheral blood lymphocytes of the mink. The homologies of the 13 mink IFN-alpha 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-alpha subtypes, most mink IFN-alpha subtypes contained two N-glycosylation sites. We expressed and purified 13 mink IFN-alpha subtypes in Escherichia coli. The cytopathic effect inhibition assay showed that all the 13 recombinant mink IFN-alpha subtypes inhibited the propagation of vesicular stomatitis virus in WISH cells, with IFN-alpha 2 and IFN-alpha 12 demonstrating the highest activities. Furthermore, recombinant mink IFN-alpha 2 and IFN-alpha 12 significantly suppressed the propagation of canine distemper virus in Vero cells, with IFN-alpha 2 demonstrating the highest activity. Conclusions: We identified the mink IFN-alpha 2 subtype as a promising candidate for the development of effective antiviral drugs.