Background: Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection is identified as the main risk factor of severe dengue diseases. The underlying mechanisms leading to severe dengue fever remain unclear. Methods: THP-1 cells were treated with an autophagy inducer (rapamycin) or inhibitor (3-methyladenine [3-MA]) and infected with DENV and DENV-ADE. In order to investigate the expression profile of autophagy-related genes in DENV-ADE and DENV direct infection of THP-1 cells, the PCR array including 84 autophagy-related genes was selected to detect the expression of related genes, and then heat map and clustergram were established by analysis software to compare the expression differences of these genes between the DENV-ADE and DENV direct infection. Results: Autophagy-inducing complex related genes ATG5 and ATG12 were upregulated, and autophagosomes were also observed by transmission electron microscopy among DENV-ADE- and DENV-infected THP-1 cells, which indicated that autophagy was involved in dengue infection. The results show that 3-MA has a significant inhibitory effect on ATG12 in THP-1 cells; on the contrary, the expression of ATG12 was upreg­ulated in THP-1 cells that were treated with rapamycin. The autophagy-related genes ESR1, INS, BNIP3, FAS, TGM2, ATG9B, and DAPK1 exhibited significant differences between DENV-ADE and DENV direct infection groups. Conclusion: In the present study, an additional mechanism of autophagy was inhibited by the autophagy inhibitor (3-MA) in DENV- and DENV-ADE-infected THP-1 cells. Our finding provided a clear link between autophagy and antibody-enhanced infection of DENV.
Intervirology

中文翻译：

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TPH-1细胞自噬介导的登革热病毒抗体依赖性增强感染的作用

背景：登革热病毒（DENV）感染的抗体依赖性增强（ADE）被确定为严重登革热疾病的主要危险因素。导致严重登革热的基本机制仍不清楚。方法：用自噬诱导剂（雷帕霉素）或抑制剂（3-甲基腺嘌呤[3-MA]）处理THP-1细胞，并感染DENV和DENV-ADE。为了研究自噬相关基因在THP-1细胞的DENV-ADE和DENV直接感染中的表达谱，选择了包含84个自噬相关基因的PCR阵列以检测相关基因的表达，然后进行热图和通过分析软件建立聚类图，以比较这些基因在DENV-ADE和DENV直接感染之间的表达差异。结果：自噬诱导的复杂相关基因ATG5和ATG12被上调，并且通过透射电子显微镜在DENV-ADE和DENV感染的THP-1细胞中也观察到自噬体，这表明自噬参与了登革热感染。结果表明3-MA对THP-1细胞中的ATG12有明显的抑制作用。相反，在用雷帕霉素处理的THP-1细胞中ATG12的表达上调。自噬相关基因ESR1，INS，BNIP3，FAS，TGM2，ATG9B和DAPK1在DENV-ADE和DENV直接感染组之间表现出显着差异。结论：在本研究中，自噬抑制剂（3-MA）在感染DENV和DENV-ADE的THP-1细胞中抑制了自噬的其他机制。我们的发现提供了自噬与DENV抗体增强感染之间的明确联系。
病毒学