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鼠类白血病病毒感染的非分裂树突细胞依赖于核氨酸

Karen Salas-Briceno¹, Wenming Zhao¹, Susan R Ross¹

¹Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, Illinois, United States of America.

|January 12, 2024

概括

鼠类白血病病毒 (MLV) 的逆转录始于细胞质,并可以继续在细胞核中,甚至在像树突细胞 (DCs) 这样的非分裂细胞中. MLV利用核孔蛋白进入核,类似于HIV.

科学领域:

病毒学病毒学
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

逆转录和脱涂是相互依赖的过程.
艾滋病毒脱涂和逆转录的精确时间和细胞位置仍在争论中.
据认为,小鼠白血病病毒 (MLV) 的复制取决于细胞分裂,其脱涂和逆转录位置尚未研究.

研究的目的:

为了研究MLV逆转录的细胞位置阶段.
为了确定MLV核进入是否需要细胞分裂.
为了比较MLV核进入机制与非分裂细胞中的HIV.

主要方法:

使用了NIH3T3细胞和初级小鼠树突细胞 (DC).
在逆转录过程中跟踪MLVRNA/DNA杂交中间体.
评估了MLV预整合复合体 (PIC) 核入口对细胞分裂的依赖性.
研究了病毒p12蛋白和核孔蛋白在MLV感染和DC中集成中的作用.
检查了MLV囊与核孔蛋白的关联.

主要成果:

最初的MLV逆转录发生在NIH3T3细胞和DC细胞的细胞质中.
在分裂NIH3T3细胞和不分裂DC细胞的核中检测到MLVRNA/DNA杂交中间体.
MLV PIC 需要细胞分裂才能进入NIH3T3细胞的核,但不能进入初级DC.
MLV可以感染不分裂的DC,其集成取决于p12蛋白.
核孔蛋白的敲除减少了MLV DNA在DC中的集成,MLV囊与NUP358和NUP62.2相互作用.

结论:

MLV逆转录在细胞质中开始,可以在核中进行.
MLV通过穿越核孔综合体来感染不分裂的DC,这是与HIV共享的机制.
在非转基因细胞中,MLV的核进入涉及与核孔蛋白相互作用.

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