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转录组分析揭示了肾综合征出血热各恢复阶段的关键分子特征。

Transcriptomic analysis reveals key molecular signatures across recovery phases of hemorrhagic fever with renal syndrome.

机构信息

Medical College, Xijing University, Xi'an, 710199, Shaanxi, People's Republic of China.

Shapingba Hospital affiliated to Chongqing University (Shapingba District People's Hospital of Chongqing), Chongqing, 400030, People's Republic of China.

出版信息

BMC Med Genomics. 2024 Sep 11;17(1):229. doi: 10.1186/s12920-024-02004-4.

DOI:10.1186/s12920-024-02004-4
PMID:39261833
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11389505/
Abstract

BACKGROUND

Hemorrhagic fever with renal syndrome (HFRS), a life-threatening zoonosis caused by hantavirus, poses significant mortality risks and lacks specific treatments. This study aimed to delineate the transcriptomic alterations during the recovery phases of HFRS.

METHODS

RNA sequencing was employed to analyze the transcriptomic alterations in peripheral blood mononuclear cells from HFRS patients across the oliguric phase (OP), diuretic phase (DP), and convalescent phase (CP). Twelve differentially expressed genes (DEGs) were validated using quantitative real-time PCR in larger sample sets.

RESULTS

Our analysis revealed pronounced transcriptomic differences between DP and OP, with 38 DEGs showing consistent expression changes across all three phases. Notably, immune checkpoint genes like CD83 and NR4A1 demonstrated a monotonic increase, in contrast to a monotonic decrease observed in antiviral and immunomodulatory genes, including IFI27 and RNASE2. Furthermore, this research elucidates a sustained attenuation of immune responses across three phases, alongside an upregulation of pathways related to tissue repair and regeneration.

CONCLUSION

Our research reveals the transcriptomic shifts during the recovery phases of HFRS, illuminating key genes and pathways that may serve as biomarkers for disease progression and recovery.

摘要

背景

肾综合征出血热(HFRS)是一种由汉坦病毒引起的危及生命的人畜共患传染病,具有较高的死亡率,且缺乏特效治疗方法。本研究旨在描述 HFRS 恢复期的转录组变化。

方法

采用 RNA 测序技术分析 HFRS 患者在少尿期(OP)、利尿期(DP)和恢复期(CP)外周血单个核细胞的转录组变化。使用实时定量 PCR 在更大的样本集中验证了 12 个差异表达基因(DEGs)。

结果

我们的分析显示 DP 和 OP 之间存在明显的转录组差异,有 38 个 DEG 在所有三个阶段表现出一致的表达变化。值得注意的是,免疫检查点基因如 CD83 和 NR4A1 呈单调递增,而抗病毒和免疫调节基因如 IFI27 和 RNASE2 则呈单调递减。此外,本研究阐明了免疫反应在三个阶段的持续衰减,同时与组织修复和再生相关的途径上调。

结论

本研究揭示了 HFRS 恢复期的转录组变化,阐明了可能作为疾病进展和恢复生物标志物的关键基因和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0048/11389505/a9895944f05d/12920_2024_2004_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0048/11389505/6b5ea50c0e93/12920_2024_2004_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0048/11389505/2559242c1d14/12920_2024_2004_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0048/11389505/a9895944f05d/12920_2024_2004_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0048/11389505/6b5ea50c0e93/12920_2024_2004_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0048/11389505/2559242c1d14/12920_2024_2004_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0048/11389505/a9895944f05d/12920_2024_2004_Fig3_HTML.jpg

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The IFN-stimulated gene IFI27 counteracts innate immune responses after viral infections by interfering with RIG-I signaling.
干扰素刺激基因IFI27通过干扰RIG-I信号传导来对抗病毒感染后的先天免疫反应。
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CD83 expressed by macrophages is an important immune checkpoint molecule for the resolution of inflammation.巨噬细胞表达的 CD83 是炎症消退的一个重要免疫检查点分子。
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Clinical and Immunological Predictors of Hemorrhagic Fever with Renal Syndrome Outcome during the Early Phase.早期肾综合征出血热临床和免疫学预测因子。
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