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从抗严重急性呼吸综合征冠状病毒2免疫反应到通过分子模拟和交叉反应引发癌症

From Anti-Severe Acute Respiratory Syndrome Coronavirus 2 Immune Response to Cancer Onset via Molecular Mimicry and Cross-Reactivity.

作者信息

Kanduc Darja

机构信息

Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, Bari, Italy.

出版信息

Glob Med Genet. 2021 Sep 7;8(4):176-182. doi: 10.1055/s-0041-1735590. eCollection 2021 Dec.

Abstract

Whether exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may predispose to the risk of cancer in individuals with no prior cancers is a crucial question that remains unclear. To confirm/refute possible relationships between exposure to the virus and ex novo insurgence of tumors, this study analyzed molecular mimicry and the related cross-reactive potential between SARS-CoV-2 spike glycoprotein (gp) antigen and human tumor-suppressor proteins.  Tumor-associated proteins were retrieved from UniProt database and analyzed for pentapeptide sharing with SARS-CoV-2 spike gp by using publicly available databases.  An impressively high level of molecular mimicry exists between SARS-CoV-2 spike gp and tumor-associated proteins. Numerically, 294 tumor-suppressor proteins share 308 pentapeptides with the viral antigen. Crucially, the shared peptides have a relevant immunologic potential by repeatedly occurring in experimentally validated epitopes. Such immunologic potential is of further relevancy in that most of the shared peptides are also present in infectious pathogens to which, in general, human population has already been exposed, thus indicating the possibility of immunologic imprint phenomena.  This article described a vast peptide overlap between SARS-CoV-2 spike gp and tumor-suppressor proteins, and supports autoimmune cross-reactivity as a potential mechanism underlying prospective cancer insurgence following exposure to SARS-CoV-2. Clinically, the findings call for close surveillance of tumor sequelae that possibly could result from the current coronavirus pandemic.

摘要

对于未曾患癌的个体而言,接触严重急性呼吸综合征冠状病毒2(SARS-CoV-2)是否会增加患癌风险,这一关键问题仍不明确。为了证实/反驳病毒暴露与肿瘤新发之间可能存在的关系,本研究分析了SARS-CoV-2刺突糖蛋白(gp)抗原与人类肿瘤抑制蛋白之间的分子模拟及相关交叉反应潜力。

从UniProt数据库中检索肿瘤相关蛋白,并通过公开可用数据库分析其与SARS-CoV-2刺突gp的五肽共享情况。

SARS-CoV-2刺突gp与肿瘤相关蛋白之间存在惊人的高水平分子模拟。从数量上看,294种肿瘤抑制蛋白与病毒抗原共享308个五肽。至关重要的是,这些共享肽通过在实验验证的表位中反复出现而具有相关的免疫潜力。这种免疫潜力更具相关性,因为大多数共享肽也存在于一般人群已经接触过的传染性病原体中,从而表明存在免疫印记现象的可能性。

本文描述了SARS-CoV-2刺突gp与肿瘤抑制蛋白之间大量的肽重叠,并支持自身免疫交叉反应作为接触SARS-CoV-2后潜在癌症发生的一种潜在机制。临床上,这些发现呼吁密切监测当前冠状病毒大流行可能导致的肿瘤后遗症。

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本文引用的文献

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The immuno-oncological challenge of COVID-19.COVID-19 的免疫肿瘤学挑战。
Nat Cancer. 2020 Oct;1(10):946-964. doi: 10.1038/s43018-020-00122-3. Epub 2020 Oct 2.
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Systemic and organ-specific immune-related manifestations of COVID-19.COVID-19 的全身性和器官特异性免疫相关表现。
Nat Rev Rheumatol. 2021 Jun;17(6):315-332. doi: 10.1038/s41584-021-00608-z. Epub 2021 Apr 26.
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Commentary: SARS-CoV-2 vaccines and cancer patients.评论:严重急性呼吸综合征冠状病毒2型疫苗与癌症患者
Ann Oncol. 2021 Apr;32(4):569-571. doi: 10.1016/j.annonc.2020.12.019. Epub 2021 Jan 12.

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