摘要
前期研究发现,细胞自噬能为人体快速提供能量,消灭掉入侵的细菌和病毒,同时对人体抗衰老有非常重要的意义;另外中性粒细胞具有免疫防御功能,并且水痘-带状疱疹病毒能引起细胞自噬,那么探讨水痘-带状疱疹病毒感染导致中性粒细胞自噬的作用机制显得尤为重要。本研究发现水痘-带状疱疹病毒感染诱导中性粒细胞发生自噬性死亡,有助于进一步研究自噬抑制剂在抗病毒感染中的应用。其中,在人神经视网膜上皮细胞(ARPE-19)中可观察到水痘-带状疱疹病毒粒子,同时可检测到带状疱疹病毒的糖蛋白E;另外,HL-60细胞经维A酸(ATRA)刺激后诱导分化成成熟的中性粒细胞,细胞核呈分叶状,RT-PCR检测细胞的CD14/CD11b表达量升高7倍,髓过氧化物酶MPO升高1.6倍;病毒感染后细胞活力随感染剂量增加逐渐降低,Beclin-1和LC3b Ⅱ的表达与病毒的量及感染时间呈现正相关,自噬抑制剂3-ma能有效抑制由病毒感染导致的中性粒细胞自噬的发生。
Autophagy can provide energy for the human body rapidly,and it can also eliminate invading bacteria and viruses. Simultaneously,it is important in the fight against aging. In addition,neutrophils have immune-defense functions,and the varicella-zoster virus(VZV)can cause autophagy of cells. Hence,it is particularly important to explore the mechanism of autophagy of neutrophils caused by VZV infection. We found that autophagy-based death of neutrophils induced by VZV infection was helpful for further study of autophagy inhibitors in anti-virus infection. Among them,complete VZV particles and glycoprotein E could be observed in human retinal pigment epithelial cells(ARPE-19). In addition,HL-60 cells were induced to differentiate into mature neutrophils-like cells by all-trans retinoic acid:the nucleus was lobulated,expression of cluster of differentiation CD14/CD11b was increased sevenfold(according to reverse transcription-polymerase chain reaction)and myeloperoxidase expression was increased 1.6-fold. After virus infection,cell viability decreased gradually with an increase in the infection dose. Expression of beclin-1 and LC3b Ⅱ was correlated positively with the amount of virus and time of infection. The autophagy inhibitor 3-ma could inhibit the neutrophil autophagy caused by virus infection.
作者
何金蓉
齐家龙
高瑞雨
靳输梅
杨旭
马雁冰
刘存宝
HE Jinrong;QI Jialong;GAO Ruiyu;JIN Shumei;YANG Xu;MA Yanbing;LIU Cunbao(Kunming Medical University,Kunming 650500,China;Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming 650000,China;Yunnan Institute of Materia Medica,Yunnan Baiyao Group Innovation and R&D Center,Yunnan Province Company KeyLaboratory for TCM and Ethnic Drug of New Drug Creation,Kunming 650111,China)
出处
《病毒学报》
CAS
CSCD
北大核心
2020年第4期643-649,共7页
Chinese Journal of Virology
基金
北京协和医学院2019年“中央高校基本科研业务费”(项目号:3332019162),题目:细胞自噬相关接头SQSTM1\p62抑制水痘-带状疱疹病毒感染的机制研究
中国医学科学院与健康科技创新工程(项目号:2017-12M-3-022),题目:新型疫苗佐剂关键技术平台建立及应用研究。
作者简介
何金蓉(1995-),女,汉族,硕士研究生,主要从事细胞死亡与肿瘤免疫相关方面的研究,E-mail:2597544335@qq.com;通讯作者:刘存宝(1984-),男,副研究员,从事免疫学研究,E-mail:cunbao_liu@imbcams.com.cn;通讯作者:马雁冰(1969-),男,研究员,从事免疫学研究,Email:yanbingma@126.com;。
