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致癌性疱疹病毒对人诱导多能干细胞的感染

Infection of human induced pluripotent stem cells by an oncogenic herpesvirus.

作者信息

Fan Jiaojiao, Lin Zhen, Zhang Huiliang, Dai Lu, Qin Zhiqiang

机构信息

Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA, United States.

出版信息

Front Cell Infect Microbiol. 2025 Mar 13;15:1563440. doi: 10.3389/fcimb.2025.1563440. eCollection 2025.

DOI:10.3389/fcimb.2025.1563440
PMID:40182776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11966036/
Abstract

OBJECTIVE

As one of the major human oncogenic viruses, Kaposi's Sarcoma-associated Herpesvirus (KSHV) is closely related to several cancers such as Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). KSHV can infect a broad tropism of human primary cells and . Embryonic stem cell-like pluripotent stem cells can be generated by the simultaneous introduction of several factors, into somatic cells, yielding induced pluripotent stem (iPS) cells. However, it remains unclear whether human induced pluripotent stem cells (hiPSCs) are permissive to KSHV and how this oncogenic virus infection may affect cellular gene profile.

METHODS

In the current study, we examined whether hiPSCs were permissive to KSHV infection. The flow cytometry was used to assess the impacts of KSHV infection on hiPSCs viability and apoptosis. The Illumina RNA-Sequencing was used to determine cellular gene profile changed in KSHV-infected hiPSCs and lytically induced cells.

RESULTS

We report that KSHV successfully establishes latent infection in hiPSCs, which can be completely induced to lytic reactivation and release infectious virions. KSHV infection arrests the growth of hiPSCs through inducing cell apoptosis. Transcriptomic analysis revealed significant changes in global cellular gene expression in KSHV-infected hiPSCs as well as lytically induced cells.

CONCLUSION

Our findings demonstrate hiPSCs as a powerful tool to explore the potential impacts of KSHV infection on stem cell functions and virus pathogenesis in stem cell differentiated cells.

摘要

目的

作为主要的人类致癌病毒之一,卡波西肉瘤相关疱疹病毒(KSHV)与卡波西肉瘤(KS)和原发性渗出性淋巴瘤(PEL)等多种癌症密切相关。KSHV能感染多种人类原代细胞。通过向体细胞同时导入几种因子可生成胚胎干细胞样多能干细胞,即诱导多能干细胞(iPS细胞)。然而,人类诱导多能干细胞(hiPSC)是否对KSHV易感以及这种致癌病毒感染如何影响细胞基因谱仍不清楚。

方法

在本研究中,我们检测了hiPSC是否对KSHV感染易感。采用流式细胞术评估KSHV感染对hiPSC活力和凋亡的影响。使用Illumina RNA测序来确定KSHV感染的hiPSC和裂解诱导细胞中细胞基因谱的变化。

结果

我们报告KSHV能在hiPSC中成功建立潜伏感染,且可被完全诱导至裂解再激活并释放感染性病毒粒子。KSHV感染通过诱导细胞凋亡抑制hiPSC的生长。转录组分析显示,KSHV感染的hiPSC以及裂解诱导细胞中整体细胞基因表达有显著变化。

结论

我们的研究结果表明,hiPSC是探索KSHV感染对干细胞功能及病毒在干细胞分化细胞中致病机制潜在影响的有力工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/a3d4d1efc024/fcimb-15-1563440-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/246fd0fe1079/fcimb-15-1563440-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/46bdd7b5f95b/fcimb-15-1563440-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/17ef293eb772/fcimb-15-1563440-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/86a8b5f9c2bb/fcimb-15-1563440-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/e86d139a689d/fcimb-15-1563440-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/363693cf406c/fcimb-15-1563440-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/d5af2cc84fa5/fcimb-15-1563440-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/258cde939747/fcimb-15-1563440-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/a3d4d1efc024/fcimb-15-1563440-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/246fd0fe1079/fcimb-15-1563440-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/46bdd7b5f95b/fcimb-15-1563440-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/17ef293eb772/fcimb-15-1563440-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/86a8b5f9c2bb/fcimb-15-1563440-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/e86d139a689d/fcimb-15-1563440-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/363693cf406c/fcimb-15-1563440-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/d5af2cc84fa5/fcimb-15-1563440-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/258cde939747/fcimb-15-1563440-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ecca/11966036/a3d4d1efc024/fcimb-15-1563440-g009.jpg

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本文引用的文献

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Stem Cell Res Ther. 2024 Oct 16;15(1):367. doi: 10.1186/s13287-024-03968-x.
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Kaposi's sarcoma-associated herpesvirus infection and its association with all-cause and cardiovascular mortality in the general adults: A prospective cohort study.卡波西肉瘤相关疱疹病毒感染及其与普通成年人全因和心血管死亡率的关系:一项前瞻性队列研究。
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YAP in development and disease: Navigating the regulatory landscape from retina to brain.
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Crosstalk between the Hippo Pathway and the Wnt Pathway in Huntington's Disease and Other Neurodegenerative Disorders.Hippo 通路与 Wnt 通路在亨廷顿病和其他神经退行性疾病中的相互作用。
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