NHC Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, 410080, China.
Department of Microbiology, School of Basic Medical Science, Central South University, Changsha, 410078, China.
Virol Sin. 2019 Jun;34(3):253-261. doi: 10.1007/s12250-019-00097-1. Epub 2019 Mar 25.
Epstein-Barr virus (EBV) is an important human dsDNA virus, which has been shown to be associated with several malignancies including about 10% of gastric carcinomas. How EBV enters an epithelial cell has been an interesting project for investigation. "Cell-in-cell" infection was recently reported an efficient way for the entry of EBV into nasopharynx epithelial cells. The present approach was to explore the feasibility of this mode for EBV infection in gastric epithelial cells and the dynamic change of host inflammatory reaction. The EBV-positive lymphoblastic cells of Akata containing a GFP tag in the viral genome were co-cultured with the gastric epithelial cells (GES-1). The infection situation was observed under fluorescence and electron microscopies. Real-time quantitative PCR and Western-blotting assay were employed to detect the expression of a few specific cytokines and inflammatory factors. The results demonstrated that EBV could get into gastric epithelial cells by "cell-in-cell" infection but not fully successful due to the host fighting. IL-1β, IL-6 and IL-8 played prominent roles in the cellular response to the infection. The activation of NF-κB and HSP70 was also required for the host antiviral response. The results imply that the gastric epithelial cells could powerfully resist the virus invader via cell-in-cell at the early stage through inflammatory and innate immune responses.
EB 病毒（EBV）是一种重要的人类双链 DNA 病毒，已被证明与多种恶性肿瘤有关，包括约 10%的胃癌。EBV 如何进入上皮细胞一直是一个有趣的研究课题。最近有报道称，“细胞内感染”是 EBV 进入鼻咽上皮细胞的一种有效途径。本研究旨在探讨这种模式在胃上皮细胞中 EBV 感染的可行性及其宿主炎症反应的动态变化。将含有病毒基因组中 GFP 标签的 EBV 阳性淋巴母细胞系 Akata 与胃上皮细胞（GES-1）共培养。通过荧光显微镜和电子显微镜观察感染情况。采用实时定量 PCR 和 Western blot 检测几种特定细胞因子和炎症因子的表达。结果表明，EBV 可以通过“细胞内感染”进入胃上皮细胞，但由于宿主的抵抗，感染并不完全成功。IL-1β、IL-6 和 IL-8 在细胞对感染的反应中起重要作用。宿主抗病毒反应也需要 NF-κB 和 HSP70 的激活。结果表明，在早期，胃上皮细胞通过炎症和先天免疫反应，通过细胞内感染可以强有力地抵抗病毒入侵。
