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Analysis of SARS-CoV-2 haplotypes and genomic sequences during 2020 in Victoria, Australia, in the context of putative deficits in innate immune deaminase anti-viral responses
Scandinavian Journal of Immunology ( IF 4.1 ) Pub Date : 2021-09-02 , DOI: 10.1111/sji.13100
Robyn A Lindley 1, 2, 3 , Edward J Steele 3, 4
Affiliation  

The SARS-CoV-2 epidemic infections in Australia during 2020 were small in number in epidemiological terms and are well described. The SARS-CoV-2 genomic sequence data of many infected patients have been largely curated in a number of publicly available databases, including the corresponding epidemiological data made available by the Victorian Department of Health and Human Services. We have critically analysed the available SARS-CoV-2 haplotypes and genomic sequences in the context of putative deficits in innate immune APOBEC and ADAR deaminase anti-viral responses. It is now known that immune impaired elderly co-morbid patients display clear deficits in interferon type 1 (α/β) and III (λ) stimulated innate immune gene cascades, of which APOBEC and ADAR induced expression are part. These deficiencies may help explain some of the clear genetic patterns in SARS-CoV-2 genomes isolated in Victoria, Australia, during the 2nd Wave (June–September, 2020). We tested the hypothesis that predicted lowered innate immune APOBEC and ADAR anti-viral deaminase responses in a significant proportion of elderly patients would be consistent with/reflected in a low level of observed mutagenesis in many isolated SARS-CoV-2 genomes. Our findings are consistent with this expectation. The analysis also supports the conclusions of the Victorian government's Department of Health that essentially one variant or haplotype infected Victorian aged care facilities where the great majority (79%) of all 820 SARS-CoV-2 associated deaths occurred. The implications of our data analysis for other localized epidemics and efficient coronavirus vaccine design and delivery are discussed.

中文翻译:

在先天免疫脱氨酶抗病毒反应假定缺陷的背景下,对 2020 年澳大利亚维多利亚州的 SARS-CoV-2 单倍型和基因组序列进行分析

从流行病学角度来看,2020 年澳大利亚发生的 SARS-CoV-2 疫情感染数量较少,且描述良好。许多感染患者的 SARS-CoV-2 基因组序列数据主要存放在许多公开数据库中,包括维多利亚州卫生与公众服务部提供的相应流行病学数据。我们在先天免疫 APOBEC 和 ADAR 脱氨酶抗病毒反应假定缺陷的背景下,对可用的 SARS-CoV-2 单倍型和基因组序列进行了批判性分析。现在已知,免疫受损的老年共病患者在 1 型干扰素 (α/β) 和 III (λ) 刺激的先天免疫基因级联中表现出明显的缺陷,其中 APOBEC 和 ADAR 诱导的表达是其中的一部分。这些缺陷可能有助于解释第二波疫情(2020 年 6 月至 9 月)期间在澳大利亚维多利亚分离出的 SARS-CoV-2 基因组中的一些清晰遗传模式。我们测试了一个假设,即预测很大一部分老年患者的先天免疫 APOBEC 和 ADAR 抗病毒脱氨酶反应降低,这与许多分离的 SARS-CoV-2 基因组中观察到的低水平突变一致/反映在这一点上。我们的研究结果与这一预期一致。该分析还支持维多利亚州政府卫生部的结论,即基本上一种变体或单倍型感染了维多利亚州的老年护理机构,所有 820 例 SARS-CoV-2 相关死亡中的绝大多数 (79%) 都发生在这些机构。讨论了我们的数据分析对其他局部流行病以及有效的冠状病毒疫苗设计和交付的影响。
更新日期:2021-10-17
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