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1. Dysregulated Interferon Response Underlying Severe COVID-19

   https://doi.org/10.3390/v12121433  

   Lopez, LeAnn; Sang, Peter C.; Tian, Yun; Sang, Yongming (December 2020, Viruses)

   null (Ed.)

   Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies. 

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2. Interferon inhibitors increase rAAV production in HEK293 cells

   https://doi.org/10.1016/j.jbiotec.2025.01.009  

   Wang, Yongdan; Fu, Qiang; Sha, Sha; Yoon, Seongkyu (March 2025, Journal of Biotechnology)
3. Circadian control of interferon-sensitive gene expression in murine skin

   https://doi.org/10.1073/pnas.1915773117  

   Greenberg, Elyse Noelani; Marshall, Michaela Ellen; Jin, Suoqin; Venkatesh, Sanan; Dragan, Morgan; Tsoi, Lam C.; Gudjonsson, Johann E.; Nie, Qing; Takahashi, Joseph S.; Andersen, Bogi (March 2020, Proceedings of the National Academy of Sciences)

   The circadian clock coordinates a variety of immune responses with signals from the external environment to promote survival. We investigated the potential reciprocal relationship between the circadian clock and skin inflammation. We treated mice topically with the Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) to activate IFN-sensitive gene (ISG) pathways and induce psoriasiform inflammation. IMQ transiently altered core clock gene expression, an effect mirrored in human patient psoriatic lesions. In mouse skin 1 d after IMQ treatment, ISGs, including the key ISG transcription factor IFN regulatory factor 7 ( Irf7), were more highly induced after treatment during the day than the night. Nuclear localization of phosphorylated-IRF7 was most prominently time-of-day dependent in epidermal leukocytes, suggesting that these cell types play an important role in the diurnal ISG response to IMQ. Mice lacking Bmal1 systemically had exacerbated and arrhythmic ISG /Irf7 expression after IMQ. Furthermore, daytime-restricted feeding, which affects the phase of the skin circadian clock, reverses the diurnal rhythm of IMQ-induced ISG expression in the skin. These results suggest a role for the circadian clock, driven by BMAL1, as a negative regulator of the ISG response, and highlight the finding that feeding time can modulate the skin immune response. Since the IFN response is essential for the antiviral and antitumor effects of TLR activation, these findings are consistent with the time-of-day–dependent variability in the ability to fight microbial pathogens and tumor initiation and offer support for the use of chronotherapy for their treatment. 

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4. Porcine Interferon Complex and Co-Evolution with Increasing Viral Pressure after Domestication

   https://doi.org/10.3390/v11060555  

   Jennings, Jordan; Sang, Yongming (June 2019, Viruses)

   Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species. To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional IFN-α/β subtypes as examples. Porcine IFN-complex thus represents an optimal model for studying IFN evolution that resulted from increasing viral pressure during domestication and industrialization. We hypothesize and justify that porcine IFN-complex may extend its functionality in antiviral and immunomodulatory activity due to its superior molecular diversity. Furthermore, these unconventional IFNs could even confer some functional and signaling novelty beyond that of the well-studied IFN-α/β subtypes. Investigations into porcine IFN-complex will further our understanding of IFN biology and promote IFN-based therapeutic designs to confront swine viral diseases. 

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5. Heparin/Collagen Coatings Improve Human Mesenchymal Stromal Cell Response to Interferon Gamma

   https://doi.org/10.1021/acsbiomaterials.9b00008  

   Castilla-Casadiego, David A.; García, José R.; García, Andrés J.; Almodovar, Jorge (May 2019, ACS Biomaterials Science & Engineering)