{"title":"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。","authors":"Liming Jiang, Qiangming Sun","doi":"10.1159/000511420","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14547,"journal":{"name":"Intervirology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000511420","citationCount":"3","resultStr":"{\"title\":\"The Role of Autophagy-Mediated Dengue Virus Antibody-Dependent Enhancement Infection of THP-1 Cells.\",\"authors\":\"Liming Jiang, Qiangming Sun\",\"doi\":\"10.1159/000511420\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":14547,\"journal\":{\"name\":\"Intervirology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2020-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1159/000511420\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Intervirology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000511420\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/11/17 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"VIROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Intervirology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000511420","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/11/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"VIROLOGY","Score":null,"Total":0}
The Role of Autophagy-Mediated Dengue Virus Antibody-Dependent Enhancement Infection of THP-1 Cells.
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.
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.
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