{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Interferon‐α16 (IFN‐α16) is a type I interferon with multifaceted roles in innate immune regulation and antiviral defense. Several lines of evidence indicate that IFN‐α16 influences disease susceptibility and progression across diverse biological contexts. For example, genetic association studies have identified IFN‐α16 variants that are linked to essential thrombocytosis and altered cytokine network profiles, suggesting that IFN‐α16 can act as a susceptibility locus in myeloproliferative disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, studies in porcine models implicate IFN‐α16 in adipogenesis and fat deposition, pointing to a role in metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Differential expression of IFN‐α subtypes has been observed during viral infections, with IFN‐α16 being dominantly expressed in the respiratory epithelial cells of patients infected with influenza A virus; such expression patterns correlate with distinct inflammatory outcomes and disease pathogenicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, genome‐wide association studies in melanoma have prioritized IFN‐α16 among a set of candidate genes involved in immune cytokine signaling, supporting its broader immunomodulatory and antitumor functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Technological advances have also enabled the isolation of antibodies that specifically recognize IFN‐α16, offering tools to dissect its individual biological activities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Recombinant production strategies utilizing a Pichia pastoris strain lacking the yapsin 1 protease have been developed to prevent proteolysis during the synthesis of human IFN‐α16 and its chimeric fusion proteins, thereby facilitating studies of its therapeutic potential."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Functionally, IFN‐α16 has demonstrated potent antiviral activity. Notably, among a panel of type I interferons, IFN‐α16 exhibited strong inhibition of Enterovirus 71 replication, and its expression is markedly elevated in advanced HIV‐1 infection, highlighting a role in viral pathogenesis and the modulation of antiviral responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the complexity and clinical relevance of IFN‐α16, which appears to contribute to antiviral defense, immune homeostasis, hematologic and metabolic regulation, as well as oncogenesis. The emerging tools for specific detection and recombinant production of IFN‐α16 are likely to foster further exploration of its unique functions and therapeutic applications.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dmitri V Gnatenko, Zhaoyan Liu, Patrick Hearing, et al. 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