The Role of Autophagy-Mediated Dengue Virus Antibody-Dependent Enhancement Infection of THP-1 Cells.

IF 3.2 4区医学 Q3 VIROLOGY

Intervirology Pub Date : 2020-01-01 Epub Date: 2020-11-17 DOI:10.1159/000511420

Liming Jiang, Qiangming Sun

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引用次数: 3

Abstract

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 upreg-ulated 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.

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自噬介导的登革热病毒抗体依赖性增强感染THP-1细胞的作用。

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。导致严重登革热的潜在机制尚不清楚。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，感染DENV和DENV- ade。为了研究自噬相关基因在DENV- ade和DENV直接感染THP-1细胞中的表达谱，选择包含84个自噬相关基因的PCR阵列检测相关基因的表达，然后通过分析软件建立热图和聚类图，比较这些基因在DENV- ade和DENV直接感染时的表达差异。结果:在DENV-ADE和denv感染的THP-1细胞中，自噬诱导复合物相关基因ATG5和ATG12表达上调，透射电镜下观察到自噬体，提示登革热感染参与了自噬。结果表明，3-MA对THP-1细胞中ATG12有明显的抑制作用;相反，在雷帕霉素处理的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直接感染组之间存在显著差异。结论:在本研究中，自噬抑制剂(3-MA)抑制了DENV-和DENV- ade感染的THP-1细胞的自噬机制。我们的发现提供了自噬和抗体增强的DENV感染之间的明确联系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Intervirology 医学-病毒学

CiteScore

5.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： ''Intervirology'' covers progress in both basic and clinical virus research, and aims to provide a forum for the various disciplines within virology. Issues publishing original papers alternate with thematic issues, focusing on clearly defined topics. This thematic concentration serves to make timely reviews, research reports and controversy easily accessible to both specialists in the field and those who want to keep track of the latest developments outside their own area of interest. In addition to original papers, regular issues publish short communications and letters to the editor to provide readers with a forum for the exchange of ideas and comments. The scope encompasses work on the molecular biology of human and animal viruses, including genome organization and regulation, and the structure and function of viral proteins. The pathogenesis, immunology, diagnosis, epidemiology, prophylaxis and therapy of viral diseases are considered.