Department of Biochemistry and Biotechnology, Council of Scientific and Industrial Research-Central Leather Research Institute (CSIR-CLRI), Chennai, India.
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, USA.
J Med Virol. 2023 Jul;95(7):e28965. doi: 10.1002/jmv.28965.
The distinct disease progression patterns of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) indicate diverse host immune responses. SARS-CoV-2 severely impairs type I interferon (IFN) cell signaling, resulting in uncontrolled late-phase lung damage in patients. For better pharmacological properties, cytokine modifications may sometimes result in a loss of biological activity against the virus. Here, we employed the genetic code expansion and engineered IFN-β, a phase II clinical cytokine with 3-amino tyrosine (IFN-β-A) that reactivates STAT2 expression in virus-infected human cells through JAK/STAT cell signaling without affecting signal activation and serum half-life. This study identified that genetically encoded IFN-β-A might stabilize the protein-receptor complex and trigger JAK-STAT cell signaling, which is a promising modality for controlling SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒 2 型（SARS-CoV-2）的独特疾病进展模式表明宿主存在不同的免疫反应。SARS-CoV-2 严重损害 I 型干扰素（IFN）细胞信号转导，导致患者晚期肺部失控性损伤。为了获得更好的药理学特性，细胞因子修饰有时会导致针对病毒的生物活性丧失。在这里，我们采用遗传密码扩展和工程化 IFN-β，一种 II 期临床细胞因子 3-氨基酪氨酸（IFN-β-A），通过 JAK/STAT 细胞信号转导重新激活病毒感染的人细胞中的 STAT2 表达，而不影响信号激活和血清半衰期。本研究表明，基因编码的 IFN-β-A 可能稳定蛋白-受体复合物并触发 JAK-STAT 细胞信号转导，这是控制 SARS-CoV-2 感染的一种有前途的方式。
