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Low compositions of human toll-like receptor 7/8-stimulating RNA motifs in the MERS-CoV, SARS-CoV and SARS-CoV-2 genomes imply a substantial ability to evade human innate immunity
PeerJ ( IF 2.7 ) Pub Date : 2021-02-24 , DOI: 10.7717/peerj.11008
Chu-Wen Yang, Mei-Fang Chen

Background The innate immune system especially Toll-like receptor (TLR) 7/8 and the interferon pathway, constitutes an important first line of defense against single-stranded RNA viruses. However, large-scale, systematic comparisons of the TLR 7/8-stimulating potential of genomic RNAs of single-stranded RNA viruses are rare. In this study, a computational method to evaluate the human TLR 7/8-stimulating ability of single-stranded RNA virus genomes based on their human TLR 7/8-stimulating trimer compositions was used to analyze 1,002 human coronavirus genomes. Results The human TLR 7/8-stimulating potential of coronavirus genomic (positive strand) RNAs followed the order of NL63-CoV > HKU1-CoV >229E-CoV ≅ OC63-CoV > SARS-CoV-2 > MERS-CoV > SARS-CoV. These results suggest that among these coronaviruses, MERS-CoV, SARS-CoV and SARS-CoV-2 may have a higher ability to evade the human TLR 7/8-mediated innate immune response. Analysis with a logistic regression equation derived from human coronavirus data revealed that most of the 1,762 coronavirus genomic (positive strand) RNAs isolated from bats, camels, cats, civets, dogs and birds exhibited weak human TLR 7/8-stimulating potential equivalent to that of the MERS-CoV, SARS-CoV and SARS-CoV-2 genomic RNAs. Conclusions Prediction of the human TLR 7/8-stimulating potential of viral genomic RNAs may be useful for surveillance of emerging coronaviruses from nonhuman mammalian hosts.

中文翻译:

MERS-CoV、SARS-CoV 和 SARS-CoV-2 基因组中人类 toll 样受体 7/8 刺激 RNA 基序的低组成意味着具有逃避人类先天免疫的能力

背景先天免疫系统,尤其是 Toll 样受体 (TLR) 7/8 和干扰素途径,构成了抵御单链 RNA 病毒的重要第一道防线。然而,对单链 RNA 病毒基因组 RNA 的 TLR 7/8 刺激潜力的大规模系统比较是罕见的。在这项研究中,基于人类 TLR 7/8 刺激三聚体组合物评估单链 RNA 病毒基因组的人类 TLR 7/8 刺激能力的计算方法用于分析 1,002 个人类冠状病毒基因组。结果冠状病毒基因组(正链)RNA的人TLR 7/8刺激潜能依次为NL63-CoV > HKU1-CoV >229E-CoV ≅ OC63-CoV > SARS-CoV-2 > MERS-CoV > SARS-冠状病毒。这些结果表明,在这些冠状病毒中,中东呼吸综合征冠状病毒、SARS-CoV 和 SARS-CoV-2 可能具有更高的逃避人类 TLR 7/8 介导的先天免疫反应的能力。使用源自人类冠状病毒数据的逻辑回归方程进行的分析表明,从蝙蝠、骆驼、猫、果子狸、狗和鸟类中分离出的 1,762 种冠状病毒基因组(正链)RNA 中的大多数表现出弱的人类 TLR 7/8 刺激潜力,相当于MERS-CoV、SARS-CoV 和 SARS-CoV-2 基因组 RNA。结论 预测病毒基因组 RNA 的人类 TLR 7/8 刺激潜力可能有助于监测来自非人类哺乳动物宿主的新出现的冠状病毒。从蝙蝠、骆驼、猫、果子狸、狗和鸟类中分离的 762 种冠状病毒基因组(正链)RNA 表现出与 MERS-CoV、SARS-CoV 和 SARS-CoV-2 基因组相当的弱人类 TLR 7/8 刺激潜力RNA。结论 预测病毒基因组 RNA 的人类 TLR 7/8 刺激潜力可能有助于监测来自非人类哺乳动物宿主的新出现的冠状病毒。从蝙蝠、骆驼、猫、果子狸、狗和鸟类中分离出的 762 种冠状病毒基因组(正链)RNA 表现出与 MERS-CoV、SARS-CoV 和 SARS-CoV-2 基因组相当的弱人类 TLR 7/8 刺激潜力RNA。结论 预测病毒基因组 RNA 的人类 TLR 7/8 刺激潜力可能有助于监测来自非人类哺乳动物宿主的新出现的冠状病毒。
更新日期:2021-02-24
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