Antiviral Activity of Transiently Expressed IFN-κ Is Cell-Associated

Most type I interferons (IFNs) are expressed by the majority of cell types in response to viral infection. In contrast, IFN-κ has been reported to have a cellular distribution limited to keratinocytes and certain lymphoid cell populations. Recombinant expressed IFN-κ has been shown previously to possess weak antiviral activity when directly compared with IFN-β. In order to expand on the antiviral potential of IFN-κ, we transiently transfected human cell lines to circumvent the need to purify recombinant proteins and to avoid the possible loss of biologic activity by the purification process. We evaluated the transcriptional signaling and antiviral activity of IFN-κ in parallel with IFN-α2b with mammalian expression vectors to express each protein transiently. Both IFN-κ and IFN-α2b exhibited comparable transcriptional and antiviral activities. However, in contrast to IFN-α2b transcriptional signaling and antiviral activity, IFN-κ activity was not detectable in conditioned cell culture medium. Subsequent experiments revealed there was a direct relationship between IFN-κ-expressing cells and antiviral activity. These results were confirmed in immunocytochemical studies. Furthermore, IFN-κ exhibited cell-associated antiviral activity against a hepatitis C virus (HCV) replicon cell line. This novel IFN signaling strategy may represent an important distinct and divergent mechanism for limiting viral infections.