Bcl2/adenovirus E1B protein-interacting protein 3 (BNIP3) plays a key role in cellular response to stress by regulating apoptosis and selective autophagy. The present study aimed to determine the effects of BNIP3 on enterovirus (EV) 71 infection-induced hand, foot and mouth disease (HFMD), and the apoptosis, autophagy and inflammatory in mice and SH-SY5Y human neuroblastoma cell line. Neonatal BALB/c mice were injected with EV 71 strain to induce the HFMD. Western blotting and ELISA were used to measure the protein expression and cytokine levels. The BNIP3 mRNA and protein levels in the brain were increased in EV 71-infected mice. By contrast, the BNIP3-knockout (KO) mice with EV 71 infection had higher health score and survival rate. BNIP3 deletion reversed the increase of cleaved-caspase 3, cleaved-caspase 8, Bax, LC3 II and LC3 II/LC3 I levels, and the decrease of Bcl2 and Bcl2/Bax and LC3 I levels in the brain of mice with EV 71 infection. The EV 71 infection-induced increase of tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, interleukin (IL)-1β, IL-6, interferon (IFN)-α and IFN-γ levels were inhibited in BNIP3-KO mice. BNIP3 knockdown with small interfering RNA (siRNA) inhibited the EV 71 infection-induced the increases of apoptosis, autophagy and inflammatory factors in SH-SY5Y cells. BNIP3 overexpression further facilitated the EV 71 infection-induced increase of these inflammatory factors in SH-SY5Y cells. These results demonstrated that BNIP3 deletion ameliorated EV 71 infection-induced HFMD via inhibiting apoptosis, autophagy and inflammation in mice. BNIP3 may be a therapeutic target for HFMD.

Bcl2 /腺病毒E1B蛋白相互作用蛋白3（BNIP3）通过调节细胞凋亡和选择性自噬在细胞对应激的反应中起关键作用。本研究旨在确定BNIP3对肠道病毒（EV）71感染诱导的手足口病（HFMD）以及小鼠和SH-SY5Y人神经母细胞瘤细胞系的凋亡，自噬和炎症的影响。新生BALB / c小鼠被注射EV 71株，以诱导手足口病。蛋白质印迹和ELISA用于测量蛋白质表达和细胞因子水平。在被EV 71感染的小鼠中，大脑中的BNIP3 mRNA和蛋白水平升高。相比之下，EV 71感染的BNIP3基因敲除（KO）小鼠具有更高的健康评分和存活率。BNIP3删除逆转了半胱天冬酶3，半胱天冬酶8，Bax，LC3 II和LC3 II / LC3 I的水平，EV 71感染小鼠大脑中Bcl2和Bcl2 / Bax以及LC3 I水平的降低。EV 71感染引起的肿瘤坏死因子（TNF）-α，单核细胞趋化蛋白（MCP）-1，白细胞介素（IL）-1β，IL-6，干扰素（IFN）-α和IFN-γ水平升高受到抑制在BNIP3-KO小鼠中。BNIP3基因敲低小干扰RNA（siRNA）抑制EV 71感染诱导SH-SY5Y细胞凋亡，自噬和炎症因子增加。BNIP3过表达进一步促进了EV 71感染诱导的SH-SY5Y细胞中这些炎症因子的增加。这些结果表明，BNIP3缺失通过抑制小鼠的细胞凋亡，自噬和炎症改善了EV 71感染引起的HFMD。BNIP3可能是手足口病的治疗靶标。