HTLV-1 Hbz 蛋白质,但不是 hbz mRNA 二次结构,对于病毒的持续性和疾病的发展至关重要
Victoria Maksimova1, Tasha Wilkie1, Susan Smith1
1Center for Retrovirus Research, Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States.
PLoS pathogens
|June 16, 2023
概括
人类T细胞白血病病毒1型 (HTLV-1) 蛋白Hbz对于T细胞不朽化并不重要,但对于病毒的持久性和成年T细胞白血病/淋巴瘤 (ATL) 在体内发展至关重要.
科学领域:
- 病毒学 病毒学
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 人类T细胞白血病病毒1型 (HTLV-1) 导致成人T细胞白血病/淋巴瘤 (ATL).
- 病毒瘤蛋白Hbz在携带者和患者中表达,这表明它在HTLV-1病变发生过程中的作用.
- 以前的研究表明,hbz蛋白对于T细胞不朽化是不可或缺的,但增强了病毒的持久性,而hbz mRNA促进了T细胞的增殖.
研究的目的:
- 研究hbz mRNA和Hbz蛋白在HTLV-1-介导的T细胞不朽化,体内持久性和疾病发展中的特定作用.
- 为了区分hbz mRNA,其二次结构和hbz蛋白的贡献.
主要方法:
- 产生突变的HTLV-1前病毒克隆,缺乏功能性的hbz mRNA或Hbz蛋白,或具有改变的hbz mRNA二次结构.
- 通过野生型和突变病毒对T细胞不朽化的体外评估.
- 在子模型和人性化免疫系统 (HIS) 小鼠中的病毒持久性和疾病发展的体内评估.
主要成果:
- 所有测试的病毒,包括那些具有改变或缺失hbz mRNA/蛋白质的病毒,都能在体外使T细胞不朽化.
- 与Hbz蛋白缺乏病毒感染的HTLV-1导致子的前病毒载荷和病毒基因表达显著降低.
- 与感染野生型或M3突变病毒的小鼠相比,感染Hbz蛋白质缺乏病毒的HIS小鼠的生存率显著增加.
结论:
- 在试验室中,对于HTLV-1-介导的T细胞不朽化,Hbz蛋白是不可缺少的.
- Hbz蛋白在体内确定HTLV-1病毒持续性和白血病发生方面发挥着至关重要的作用.
- 改变hbz mRNA二次结构或其损失不会显著影响体外T细胞不朽化.
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