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IFN-λ1 在体外对一系列 RNA 病毒具有不同水平的抗病毒活性。

IFN-λ1 Displays Various Levels of Antiviral Activity In Vitro in a Select Panel of RNA Viruses.

机构信息

Smorodintsev Research Institute of Influenza, Russian Ministry of Health, 197376 St. Petersburg, Russia.

Institute of Biomedical Systems and Biotechnologies, Peter the Great St. Petersburg Polytechnic University, 195251 St. Petersburg, Russia.

出版信息

Viruses. 2021 Aug 12;13(8):1602. doi: 10.3390/v13081602.

Abstract

Type III interferons (lambda IFNs) are a quite new, small family of three closely related cytokines with interferon-like activity. Attention to IFN-λ is mainly focused on direct antiviral activity in which, as with IFN-α, viral genome replication is inhibited without the participation of immune system cells. The heterodimeric receptor for lambda interferons is exposed mainly on epithelial cells, which limits its possible action on other cells, thus reducing the likelihood of developing undesirable side effects compared to type I IFN. In this study, we examined the antiviral potential of exogenous human IFN-λ1 in cellular models of viral infection. To study the protective effects of IFN-λ1, three administration schemes were used: 'preventive' (pretreatment); 'preventive/therapeutic' (pre/post); and 'therapeutic' (post). Three IFN-λ1 concentrations (from 10 to 500 ng/mL) were used. We have shown that human IFN-λ1 restricts SARS-CoV-2 replication in Vero cells with all three treatment schemes. In addition, we have shown a decrease in the viral loads of CHIKV and IVA with the 'preventive' and 'preventive/therapeutic' regimes. No significant antiviral effect of IFN-λ1 against AdV was detected. Our study highlights the potential for using IFN-λ as a broad-spectrum therapeutic agent against respiratory RNA viruses.

摘要

III 型干扰素(lambda IFN)是一个相当新的、小的家族,由三种具有类似干扰素活性的密切相关的细胞因子组成。对 IFN-λ 的关注主要集中在直接抗病毒活性上,与 IFN-α 一样,病毒基因组复制被抑制,而无需免疫系统细胞的参与。lambda 干扰素的异源二聚体受体主要在上皮细胞上表达,这限制了其在其他细胞上的可能作用,从而降低了与 I 型 IFN 相比产生不良副作用的可能性。在这项研究中,我们研究了外源性人 IFN-λ1 在病毒感染的细胞模型中的抗病毒潜力。为了研究 IFN-λ1 的保护作用,我们使用了三种给药方案:“预防”(预处理);“预防/治疗”(预/后)和“治疗”(后)。使用了三种 IFN-λ1 浓度(从 10 到 500 ng/mL)。我们表明,人 IFN-λ1 在用三种治疗方案限制了 Vero 细胞中的 SARS-CoV-2 复制。此外,我们还表明,在用“预防”和“预防/治疗”方案时,CHIKV 和 IVA 的病毒载量减少。未检测到 IFN-λ1 对 AdV 的显著抗病毒作用。我们的研究强调了 IFN-λ 作为一种针对呼吸道 RNA 病毒的广谱治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5072/8402797/6f53a0b90b5a/viruses-13-01602-g001.jpg

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