Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Cell Rep. 2022 May 10;39(6):110799. doi: 10.1016/j.celrep.2022.110799. Epub 2022 Apr 21.
Although vaccines and monoclonal antibody countermeasures have reduced the morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, variants with constellations of mutations in the spike gene jeopardize their efficacy. Accordingly, antiviral interventions that are resistant to further virus evolution are needed. The host-derived cytokine interferon lambda (IFN-λ) has been proposed as a possible treatment based on studies in human coronavirus 2019 (COVID-19) patients. Here, we show that IFN-λ protects against SARS-CoV-2 B.1.351 (Beta) and B.1.1.529 (Omicron) variants in three strains of conventional and human ACE2 transgenic mice. Prophylaxis or therapy with nasally delivered IFN-λ2 limits infection of historical or variant SARS-CoV-2 strains in the upper and lower respiratory tracts without causing excessive inflammation. In the lung, IFN-λ is produced preferentially in epithelial cells and acts on radio-resistant cells to protect against SARS-CoV-2 infection. Thus, inhaled IFN-λ may have promise as a treatment for evolving SARS-CoV-2 variants that develop resistance to antibody-based countermeasures.
尽管疫苗和单克隆抗体对策降低了严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染相关的发病率和死亡率，但刺突基因中存在突变组合的变体危及了它们的疗效。因此，需要具有抵抗病毒进一步进化的抗病毒干预措施。基于人类冠状病毒 2019（COVID-19）患者的研究，宿主来源的细胞因子干扰素 lambda（IFN-λ）被提议作为一种可能的治疗方法。在这里，我们表明 IFN-λ 可预防三种普通和人类 ACE2 转基因小鼠中 SARS-CoV-2 B.1.351（Beta）和 B.1.1.529（Omicron）变体的感染。鼻腔给予 IFN-λ2 的预防或治疗可限制上呼吸道和下呼吸道中历史或变体 SARS-CoV-2 株的感染，而不会引起过度炎症。在肺部，IFN-λ 优先在上皮细胞中产生，并作用于辐射抗性细胞以防止 SARS-CoV-2 感染。因此，吸入 IFN-λ 可能有望成为治疗对基于抗体的对策产生耐药性的不断进化的 SARS-CoV-2 变体的方法。
