Characterization of interferon-alpha 13, a novel constitutive murine interferon-alpha subtype

Type-I interferons (IFNs), also called IFNs-alpha/beta, are a family of cytokines induced by viral infection and are primarily involved in antiviral defense of the cells. IFNs-alpha/beta were also reported to be produced constitutively at low levels in mouse and human cells. These so-called endogenous or constitutive IFNs are thought to exert important homeostatic functions in the uninfected host. By searching IFN genes that were not repressed by the leader protein of Theiler's virus, we identified three uncharacterized IFN-alpha genes that are constitutively expressed in uninfected mouse cells, in vitro and in vivo. Two of these genes corresponded to pseudogenes and were tentatively called IFN-alpha(psi2) and IFN-alpha(psi3). IFN-alpha(psi2) transcripts are the most abundant IFN-alpha transcripts detected in several mouse organs in the absence of viral infection. The third gene codes for a new IFN-alpha subtype called IFN-alpha13, which exhibits acid-stable antiviral activity against Theiler's virus, Mengo virus, and vesicular stomatitis virus. IFN-alpha13 displays unusual characteristics, suggesting that it might have a particular function. Firstly, it is transcribed constitutively, independent of viral infection and of interferon regulatory factor-7 induction. Secondly, it contains two N-glycosylation sites, in contrast to other murine IFN-alpha subtypes that contain either one or no N-glycosylation site. In addition to the genes described here above, several other IFN-alpha subtype genes, including a new gene (IFN-alpha14), were expressed in tissues of uninfected mice. In contrast to IFN-alpha13, IFN-alpha14 was found to lack N-glycosylation and have its expression induced in response to viral infection.