Unconventional nucleus export and secondary necrosis of human leukemia T lymphocytes (Jurkat cells) transfected with HIV-1 LTR CAT-TAT-72: ultrastructural assessment.

IF 1.2 4区 医学 Q4 MICROSCOPY
Ultrastructural Pathology Pub Date : 2025-01-01 Epub Date: 2025-08-31 DOI:10.1080/01913123.2025.2545858
Jacques Gilloteaux, Etienne de Harven, John Koch
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引用次数: 0

Abstract

Efficient transcriptional activation and replication of the human immunodeficiency virus (HIV-1) is dependent on Tat protein. Initial observations have shown that human leukemia T lymphocytes (Jurkat cells aka Wild type or WT) transfected with HIV-1 LTR CAT TAT-72 plasmid as Control (CTJ) cells, and CTJ transfected by electroporation with pcDNA3-pU3R-CAT-TAT-72 (TJ cells) showed growth and maintenance resulting in giant and small cells with accumulated corpses. The lack of fine structure in Jurkat cells and both transfected cells aimed at us to verify their respective ultrastructure modifications. Scanning and transmission electron microscopy showed evident Cajal bodies in CTJ cells compared with WT cells and revealed unconventional nucleus export of viral-associated transcripts where eruption of the nucleus envelope spilled content from the perinuclear space toward exocytosis via a lined membranous channel continuum of endoplasmic reticulum - mitochondria envelope. TJ cells grew as small and giant cells where giant cells bore virological synapses stimulating apoptogenic impetus but where cell demise included osmotic bursts mostly resulted into secondary necrosis. Jurkat transfected cells could model in vitro resilient human T lymphocytes (or other infected cells) that remain factories of expressed HIV-1 virus proteins such as Tat, secreted and captured by other cells as in viral infections and can form giant cells. Those Tat and other transcripts induced cell demise, as in vivo those HIV-1 viral proteins and traces can amplify infectivity as in AIDS, altering primary lymphoid organs and secondary lymphoid organs.

转染HIV-1 LTR CAT-TAT-72的人白血病T淋巴细胞(Jurkat细胞)的非常规核输出和继发性坏死:超微结构评价
人类免疫缺陷病毒(HIV-1)的有效转录激活和复制依赖于Tat蛋白。初步观察表明,用HIV-1 LTR CAT TAT-72质粒转染的人类白血病T淋巴细胞(Jurkat细胞,又名野生型或WT)作为对照(CTJ)细胞,以及用pcDNA3-pU3R-CAT-TAT-72质粒电穿孔转染的CTJ细胞(TJ细胞)显示出生长和维持,导致巨细胞和小细胞积累尸体。Jurkat细胞和两种转染细胞缺乏精细结构,目的是验证它们各自的超微结构修饰。扫描电镜和透射电镜显示,与WT细胞相比,CTJ细胞中有明显的Cajal小体,并显示出病毒相关转录物的非常规细胞核输出,其中核膜的爆发将内容物从核周空间溢出,通过内质网-线粒体包膜的内衬膜通道向胞外分泌。TJ细胞生长为小细胞和巨细胞,巨细胞具有刺激凋亡的病毒学突触,但细胞死亡包括渗透破裂,主要导致继发性坏死。Jurkat转染的细胞可以在体外模拟有弹性的人类T淋巴细胞(或其他受感染的细胞),这些细胞仍然是表达HIV-1病毒蛋白(如Tat)的工厂,在病毒感染中被其他细胞分泌和捕获,并可以形成巨细胞。这些Tat和其他转录本诱导细胞死亡,就像在体内,这些HIV-1病毒蛋白和痕迹可以像在艾滋病中一样增强传染性,改变原发性淋巴器官和继发性淋巴器官。
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来源期刊
Ultrastructural Pathology
Ultrastructural Pathology 医学-病理学
CiteScore
2.00
自引率
10.00%
发文量
40
审稿时长
6-12 weeks
期刊介绍: Ultrastructural Pathology is the official journal of the Society for Ultrastructural Pathology. Published bimonthly, we are the only journal to be devoted entirely to diagnostic ultrastructural pathology. Ultrastructural Pathology is the ideal journal to publish high-quality research on the following topics: Advances in the uses of electron microscopic and immunohistochemical techniques Correlations of ultrastructural data with light microscopy, histochemistry, immunohistochemistry, biochemistry, cell and tissue culturing, and electron probe analysis Important new, investigative, clinical, and diagnostic EM methods.
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