MAL表达对HIV感染者疾病进展的影响及相关机制研究  

Regulatory roles of MAL in the disease progression of HIV infection and the molecular mechanisms

作　　者：董原[1] 林怡[1] 周磊明[2] 肖健 王盈[1] DONG Yuan;LIN Yi;ZHOU Leiming;XIAO Jian;WANG Ying(Department of AIDS and STD,Shanghai Municipal Center for Disease Control and Prevention;Guangxi Key Laboratory of Translational Medicine for Treating High-Incidence Infectious Diseases with Integrative Medicine)

机构地区：[1]上海市疾病预防控制中心结核病和艾滋病防治所艾滋病检测实验室,200336 [2]上海市疾病预防控制中心艾滋病性病麻风病防治科,200336 [3]广西高发传染病中西医结合转化医学重点实验室,南宁530022

出　　处：《免疫学杂志》2020年第8期713-719,共7页Immunological Journal

基　　金：国家自然科学基金青年项目(81602905);上海市卫生系统优秀青年医学人才培养计划(2018YQ57);2017年度上海市卫生和计划生育委员会科研课题(20164Y0245)。

摘　　要：目的研究T淋巴细胞成熟相关蛋白(MAL)对HIV感染者疾病进展的影响,并探索其相关分子机制。方法利用流式细胞术检测MAL在HIV感染不同阶段T细胞上的表达,分析MAL表达水平与疾病进展的相关性;通过细胞系和体外刺激模型研究MAL对细胞因子分泌、细胞增殖的影响;利用细胞系模型检测MAL对HIV病毒包装的影响。结果MAL表达水平与HIV感染者CD4^+T细胞绝对数和CD4^+T/CD8^+T比值呈显著正相关,高CD4^+T细胞组MAL的表达显著高于低CD4^+T细胞组;MAL敲除下调T细胞IL-2分泌,对细胞增殖影响不明显;MAL过表达对病毒总量无影响,但可提高HIV在细胞内的感染效率。结论本研究发现MAL表达水平与HIV感染者疾病进展呈显著负相关,其下调表达可抑制IL-2分泌,从而影响T细胞活性;MAL过表达可提高HIV的感染效率,机制有待进一步研究。This study was performed to analyze the relationship between T-cell differentiation protein(MAL)expression and the disease progression of HIV^+subjects and to explore the molecular mechanisms.MAL expression on T cells from HIV^+subjects of different disease progression were examined by flow cytometry to analyze the effect of MAL in T cell functions,including cell proliferation and cytokine secretion.The influence of MAL on HIV packaging in 293 T and Jurkat cell lines were also tested.Data showed that MAL expression was significantly associated with CD4^+T cell count and CD4^+T/CD8^+T ratio,and MAL expression is significantly higher in high CD4^+T cell count group,compared to low CD4^+T cell count group.MAL knockdown could down-regulate IL-2 secretion.Moreover,MAL over-expression could enhance HIV packaging efficiency in HIV infected cells.In conclusion,MAL expression is negatively associated with HIV disease progression,and MAL downregulation represses IL-2 secretion.MAL could enhance the infection efficiency of HIV,and the mechanism needs further study.

关 键 词：HIV-1 T淋巴细胞成熟相关蛋白 疾病进展 T淋巴细胞 病毒包装 

分 类 号：R392.1[医药卫生—免疫学]