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COVID-19 病患者死亡率:主要组织相容性复合体 (MHC) 与严重急性呼吸综合征 2 (SARS-CoV-2) 变体的关联。

Mortality in COVID-19 disease patients: Correlating the association of major histocompatibility complex (MHC) with severe acute respiratory syndrome 2 (SARS-CoV-2) variants.

机构信息

ImmunoSurgery Unit, Champalimaud Centre for the Unknown, Avenida Brasília, 1400-038 Lisbon, Portugal.

Lisbon Centre for Blood and Transplantation (Instituto Português do Sangue e Transplantação, IPST, Lisbon, Portugal.

出版信息

Int J Infect Dis. 2020 Sep;98:454-459. doi: 10.1016/j.ijid.2020.07.016. Epub 2020 Jul 18.

Abstract

Genetic factors such as the HLA type of patients may play a role in regard to disease severity and clinical outcome of patients with COVID-19. Taking the data deposited in the GISAID database, we made predictions using the IEDB analysis resource (TepiTool) to gauge how variants in the SARS-CoV-2 genome may change peptide binding to the most frequent MHC-class I and -II alleles in Africa, Asia and Europe. We caracterized how a single mutation in the wildtype sequence of of SARS-CoV-2 could influence the peptide binding of SARS-CoV-2 variants to MHC class II, but not to MHC class I alleles. Assuming the ORF8 (L84S) mutation is biologically significant, selective pressure from MHC class II alleles may select for viral varients and subsequently shape the quality and quantity of cellular immune responses aginast SARS-CoV-2. MHC 4-digit typing along with viral sequence analysis should be considered in studies examining clinical outcomes in patients with COVID-19.

摘要

遗传因素,如患者的 HLA 类型,可能在 COVID-19 患者的疾病严重程度和临床结局方面发挥作用。我们利用 GISAID 数据库中存储的数据,使用 IEDB 分析资源(TepiTool)进行预测,以评估 SARS-CoV-2 基因组中的变异如何改变与非洲、亚洲和欧洲最常见的 MHC Ⅰ类和Ⅱ类等位基因的肽结合。我们描述了 SARS-CoV-2 野生型序列中的单个突变如何影响 SARS-CoV-2 变异与 MHC Ⅱ类而非 MHC Ⅰ类等位基因的肽结合。假设 ORF8(L84S)突变具有生物学意义,那么 MHC Ⅱ类等位基因的选择压力可能会选择病毒变异体,并随后塑造针对 SARS-CoV-2 的细胞免疫反应的质量和数量。在研究 COVID-19 患者的临床结局时,应考虑 MHC 四位数字分型和病毒序列分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aeb6/7368421/905d2d17965b/gr1_lrg.jpg

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