Interferons (IFN) are a family of cytokines with potent antiviral, antiproliferative and immunomodulatory properties, classified based on their binding specificity to cell surface receptors . Human IFNA2 was originally cloned in the early ‘80s and now more than a dozen closely related IFN alpha subtypes have been identified in both the human and mouse genome, each sharing about 80% amino acid (aa) sequence homology . Structurally, type I IFNs belong to the class of five helical bundle cytokines, with the IFNA subtypes containing 2 conserved disulfide bonds. The extracellular domain (ECD) of mature human IFNA14, shares 58% aa sequence identity with mouse IFNA14. The type I IFNs bind to the interferon alpha receptor (IFNAR), which consists of two subunits: IFNAR1 (alpha subunit) and IFNAR2 (beta-subunit). Individual IFNA subtypes are known to display unique efficacies to viral protection, and IFNA14 has been shown to be a strong inducer of IFN-stimulated genes and anti-viral protection . IFNA14 has been shown to be potent against HIV-1 by up regulating the transcription of two intrinsic restriction factors with well-established anti-HIV-1 activity, MX2 and tetherin.