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基于细胞反卷积的全血转录组综合时间序列网络揭示了针对猪繁殖与呼吸综合征病毒感染的全身抗病毒活性和细胞特异性免疫变化。

Cell deconvolution-based integrated time-series network of whole blood transcriptome reveals systemic antiviral activities and cell-specific immunological changes against PRRSV infection.

作者信息

Lim Byeonghwi, Lim Chiwoong, Jang Min-Jae, Seo Young-Jun, Kim Do-Young, Tuggle Christopher K, Lim Kyu-Sang, Kim Jun-Mo

机构信息

Functional Genomics & Bioinformatics Laboratory, Department of Animal Science and Technology, Chung-Ang University, Anseong, Gyeonggi-do, 17546, Republic of Korea.

Department of Animal Science, Iowa State University, Ames, IA, 50011, USA.

出版信息

Vet Res. 2025 Jan 22;56(1):19. doi: 10.1186/s13567-025-01451-w.

DOI:10.1186/s13567-025-01451-w
PMID:39844283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11755918/
Abstract

Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses in the swine industry. However, the molecular mechanisms behind the common and cell type-specific systemic responses during PRRS virus (PRRSV) infection are not well understood. In this study, we collected viremia data, antibody levels, and whole-blood RNA-seq data obtained from eight PRRSV-infected piglets. We utilised a cell deconvolution approach to calculate cell type enrichment, constructed a time-serial gene co-expression network with differentially expressed genes, and conducted functional annotations. Three significant modules were identified within the network. The changes associated with viremia revealed an upregulated expression of genes related to antiviral activity. In the T-cell- and NK-cell-specific modules, infection led to an increased T-cell population and upregulation of genes related to T-cell defence responses. Conversely, in the monocyte- and neutrophil-specific module, genes involved in inflammatory responses were downregulated due to a decrease in monocyte proportion. This study highlights the time-series antiviral activities associated with viremia and the transcriptomic changes associated with immune responses in specific cell types. The findings provide comprehensive insights into host responses to PRRSV infection, including diagnostic biomarkers.

摘要

猪繁殖与呼吸综合征(PRRS)给养猪业造成了巨大的经济损失。然而,猪繁殖与呼吸综合征病毒(PRRSV)感染期间常见的和细胞类型特异性全身反应背后的分子机制尚未完全清楚。在本研究中,我们收集了8只感染PRRSV的仔猪的病毒血症数据、抗体水平和全血RNA测序数据。我们采用细胞反卷积方法计算细胞类型富集度,构建了包含差异表达基因的时间序列基因共表达网络,并进行了功能注释。在该网络中识别出了三个显著模块。与病毒血症相关的变化显示抗病毒活性相关基因的表达上调。在T细胞和自然杀伤细胞特异性模块中,感染导致T细胞数量增加以及与T细胞防御反应相关基因的上调。相反,在单核细胞和中性粒细胞特异性模块中,由于单核细胞比例降低,参与炎症反应的基因下调。本研究突出了与病毒血症相关的时间序列抗病毒活性以及特定细胞类型中与免疫反应相关的转录组变化。这些发现为宿主对PRRSV感染的反应提供了全面的见解,包括诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63a/11755918/82ed950d4901/13567_2025_1451_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63a/11755918/82ed950d4901/13567_2025_1451_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63a/11755918/db6139449b4b/13567_2025_1451_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63a/11755918/99db36374584/13567_2025_1451_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63a/11755918/8107aa38c597/13567_2025_1451_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63a/11755918/09d3411840c4/13567_2025_1451_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e63a/11755918/82ed950d4901/13567_2025_1451_Fig5_HTML.jpg

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Front Immunol. 2023 Jun 20;14:1159970. doi: 10.3389/fimmu.2023.1159970. eCollection 2023.
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Integrative time-serial networks for genome-wide lncRNA-mRNA interactions reveal interferon-inducible antiviral and T-cell receptor regulations against PRRSV infection.整合时间序列网络分析全基因组长链非编码 RNA-信使 RNA 相互作用揭示了干扰素诱导的抗病毒和 T 细胞受体对 PRRSV 感染的调控作用。
Dev Comp Immunol. 2023 Oct;147:104759. doi: 10.1016/j.dci.2023.104759. Epub 2023 Jun 12.
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Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV.
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