The PDZ domain of the E protein in SARS-CoV induces carcinogenesis and poor prognosis in LUAD.

IF 2.6 4区医学 Q3 IMMUNOLOGY

Microbes and Infection Pub Date : 2024-06-22 DOI:10.1016/j.micinf.2024.105381

Shun Li, Jinxuan Wang, Xiaozhen Dai, Churong Li, Tao Li, Long Chen

{"title":"The PDZ domain of the E protein in SARS-CoV induces carcinogenesis and poor prognosis in LUAD.","authors":"Shun Li, Jinxuan Wang, Xiaozhen Dai, Churong Li, Tao Li, Long Chen","doi":"10.1016/j.micinf.2024.105381","DOIUrl":null,"url":null,"abstract":"Background: In both lung adenocarcinoma (LUAD) and severe acute respiratory syndrome (SARS), uncontrolled inflammation can be detected in lung tissue. The PDZ-binding motif (PBM) in the SARS-CoV-1 E protein has been demonstrated to be a virulence factor that induces a cytokine storm.Methods: To identify gene expression fluctuations induced by PBM, microarray sequencing data of lung tissue infected with wild-type (SARS-CoV-1-E-wt) or recombinant virus (SARS-CoV-1-E-mutPBM) were analyzed, followed by functional enrichment analysis. To understand the role of the screened genes in LUAD, overall survival and immune correlation were calculated.Results: A total of 12 genes might participate in the initial and developmental stages of LUAD through expression variation and mutation. Moreover, dysregulation of a total of 12 genes could lead to a poorer prognosis. In addition, the downregulation of MAMDC2 and ITGA8 by PBM could also affect patient prognosis. Although the conserved PBM (-D-L-L-V-) can be found at the end of the carboxyl terminus in multiple E proteins of coronaviruses, the specific function of each protein depends on the entire amino acid sequence.Conclusions: In summary, PBM containing the SARS-CoV-1 E protein promoted the carcinogenesis of LUAD by dysregulating important gene expression profiles and subsequently influencing the immune response and overall prognosis.","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbes and Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.micinf.2024.105381","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: In both lung adenocarcinoma (LUAD) and severe acute respiratory syndrome (SARS), uncontrolled inflammation can be detected in lung tissue. The PDZ-binding motif (PBM) in the SARS-CoV-1 E protein has been demonstrated to be a virulence factor that induces a cytokine storm.

Methods: To identify gene expression fluctuations induced by PBM, microarray sequencing data of lung tissue infected with wild-type (SARS-CoV-1-E-wt) or recombinant virus (SARS-CoV-1-E-mutPBM) were analyzed, followed by functional enrichment analysis. To understand the role of the screened genes in LUAD, overall survival and immune correlation were calculated.

Results: A total of 12 genes might participate in the initial and developmental stages of LUAD through expression variation and mutation. Moreover, dysregulation of a total of 12 genes could lead to a poorer prognosis. In addition, the downregulation of MAMDC2 and ITGA8 by PBM could also affect patient prognosis. Although the conserved PBM (-D-L-L-V-) can be found at the end of the carboxyl terminus in multiple E proteins of coronaviruses, the specific function of each protein depends on the entire amino acid sequence.

Conclusions: In summary, PBM containing the SARS-CoV-1 E protein promoted the carcinogenesis of LUAD by dysregulating important gene expression profiles and subsequently influencing the immune response and overall prognosis.

查看原文本刊更多论文

SARS-CoV中E蛋白的PDZ域诱导LUAD的癌变和不良预后

背景：在肺腺癌（LUAD）和严重急性呼吸系统综合征（SARS）中，都可以在肺组织中检测到不受控制的炎症。SARS-CoV-1 E 蛋白中的 PDZ 结合基序（PBM）已被证实是诱导细胞因子风暴的毒力因子：为了确定PBM诱导的基因表达波动，我们分析了野生型（SARS-CoV-1-E-wt）或重组病毒（SARS-CoV-1-E-mutPBM）感染的肺组织的芯片测序数据，然后进行了功能富集分析。为了解筛选出的基因在 LUAD 中的作用，计算了总生存率和免疫相关性：结果：共有12个基因可能通过表达变异和突变参与了LUAD的初期和发展阶段。结果：共有 12 个基因可能通过表达变异和突变参与了 LUAD 的初始和发展阶段，而且这 12 个基因的失调可能导致较差的预后。此外，PBM 对 MAMDC2 和 ITGA8 的下调也会影响患者的预后。尽管在冠状病毒的多种E蛋白的羧基末端都能找到保守的PBM（-D-L-L-V-），但每种蛋白的特定功能都取决于整个氨基酸序列：总之，含有SARS-CoV-1 E蛋白的PBM通过调节重要的基因表达谱，进而影响免疫反应和整体预后，促进了LUAD的癌变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Microbes and Infection 医学-病毒学

CiteScore

12.60

自引率

1.70%

发文量

审稿时长

40 days

期刊介绍： Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular: the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms. the immune response to infection, including pathogenesis and host susceptibility. emerging human infectious diseases. systems immunology. molecular epidemiology/genetics of host pathogen interactions. microbiota and host "interactions". vaccine development, including novel strategies and adjuvants. Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal. Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.