Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.
Regulation of Viral Replication, Apoptosis and Pro-Inflammatory Responses by 17-AAG during Chikungunya Virus Infection in Macrophages.
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DOI：
10.3390/v9010003
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发表时间：
2017-01-06
期刊：
影响因子：
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通讯作者：
Chattopadhyay S
中科院分区：
文献类型：
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作者：
Nayak TK;Mamidi P;Kumar A;Singh LP;Sahoo SS;Chattopadhyay S;Chattopadhyay S
基孔肯雅病毒(CHIKV)感染由于最近在世界范围内流行和缺乏控制措施，再次成为一个主要的公共卫生问题。虽然已知CHIKV可感染巨噬细胞，但对CHIKV复制、细胞凋亡和对巨噬细胞的免疫反应的调节尚不清楚。相应地，用CHIKV感染小鼠巨噬细胞系Raw264.7细胞，用流式细胞仪和空斑试验分别检测病毒的复制和新病毒的释放。此外，通过流式细胞仪、Western印迹和ELISA法研究了宿主的免疫调节和细胞凋亡。我们目前的研究结果表明，CHIKV蛋白的表达在8HPI时达到最大值，新病毒后代的释放在12HPI左右显著增加。在CHIKV感染的巨噬细胞中，Annexin V结合、caspase-3、caspase-9和caspase-8的裂解均被诱导，提示CHIKV感染的巨噬细胞通过内源性和外源性途径激活了细胞凋亡。在感染过程中，促炎症介质(TNF和IL-6)、MHC-I/II和B7.2(CD86)的表达也随着时间的推移而上调。此外，17-AAG是一种潜在的HSP90抑制剂，可显著调节CHIKV感染、细胞凋亡和宿主巨噬细胞的促炎细胞因子/趋化因子的产生。因此，目前的发现可能为CHIKV疾病生物学中的治疗意义带来新的见解。
Chikungunya virus (CHIKV) infection has re-emerged as a major public health concern due to its recent worldwide epidemics and lack of control measures. Although CHIKV is known to infect macrophages, regulation of CHIKV replication, apoptosis and immune responses towards macrophages are not well understood. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV and viral replication as well as new viral progeny release was assessed by flow cytometry and plaque assay, respectively. Moreover, host immune modulation and apoptosis were studied through flow cytometry, Western blot and ELISA. Our current findings suggest that expression of CHIKV proteins were maximum at 8 hpi and the release of new viral progenies were remarkably increased around 12 hpi. The induction of Annexin V binding, cleaved caspase-3, cleaved caspase-9 and cleaved caspase-8 in CHIKV infected macrophages suggests activation of apoptosis through both intrinsic and extrinsic pathways. The pro-inflammatory mediators (TNF and IL-6) MHC-I/II and B7.2 (CD86) were also up-regulated during infection over time. Further, 17-AAG, a potential HSP90 inhibitor, was found to regulate CHIKV infection, apoptosis and pro-inflammatory cytokine/chemokine productions of host macrophages significantly. Hence, the present findings might bring new insight into the therapeutic implication in CHIKV disease biology.