烟酰胺(NAM)对SIV/SHIV感染猴CD4^(+)T细胞中潜伏病毒的激活作用研究  

Reactivation effect of NAM on latent reservoir in CD4^(+)T cells from SIV/SHIV-infected monkeys

作　　者：党翠 陆佳涵 魏强 薛婧 丛喆 DANG Cui;LU Jiahan;WEI Qiang;XUE Jing;CONG Zhe(Peking Union Medical College(PUMC)&Institute of Laboratory Animal Science,Comparative Medicine Center,Chinese Academy of Medical Sciences(CAMS),NHC Key Laboratory of Human Disease Comparative Medicine,Key Laboratory of Human Diseases Animal Models,State administration of Traditional Chinese medicine,Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases,Beijing 100021,China)

机构地区：[1]中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,国家卫生健康委员会人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,新发再发传染病动物模型研究北京市重点实验室,北京100021

出　　处：《中国比较医学杂志》2022年第5期23-28,46,共7页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金(81971944);中国医学科学院医学与健康科技创新工程重大协同创新项目(2021-I2M-1-037)。

摘　　要：目的 探讨烟酰胺(NAM)对SIV/SHIV感染猴CD4^(+)T细胞中潜伏病毒的激活效果及其机制。方法 采集血浆病毒载量长期阴性的SIV/SHIV感染猴外周血,分选CD4^(+)T细胞,分别加入NAM、GS-9620、Prostratin等潜伏感染激活剂,检测细胞上清病毒载量,流式分析CD4^(+)T细胞的表面活化分子CD69、CD38、HLA-DR以及辅助受体CXCR4、CCR5的表达情况,蛋白质印迹法(Western blot)检测核内抗原SIRT1表达量的变化。结果 NAM对SIV/SHIV感染猴CD4^(+)T细胞中潜伏病毒具有一定的激活效果,与GS-9620联合使用,可以更大程度的激活潜伏病毒。同时,并不引起T细胞广泛活化,虽小幅上调辅助受体CXCR4的表达,但并不影响CCR5的表达,可以显著降低细胞核内抗原SIRT1的表达。结论 NAM可以作为潜伏感染激活剂的一个选择。Objective To investigate the reactivation effect of nicotinamide(NAM) on latent virus in SIV/SHIV-infected monkey CD4^(+)T cells. Methods Peripheral blood from five SIV/SHIV-infected rhesus monkeys was collected with undetectable virus loads for at least half a year. CD4^(+)T cells were sorted and treated with latency-reversing agents accompanied by monitoring of viral loads in supernatants and changes in activated T cell surface markers and coreceptors CXCR4 and CCR5 on CD4^(+)T cells. Changes in nuclear antigen SIRT1 were detected by Western blot. Results NAM had a good activation effect on latent virus in SIV/SHIV-infected monkey CD4^(+)T cells and reached a higher level combined with GS-9620. This did not cause extensive activation of T cells and had no influence on CCR5 expression, while CXCR4 expression was slightly upregulated. NAM significantly reduced expression of nuclear antigen SIRT1. Conclusions NAM is a good choice for a latency-reversing agent.

关 键 词：烟酰胺 GS-9620 潜伏感染激活剂 SIV SHIV 潜伏库 

分 类 号：R-33[医药卫生]