Hsieh Tzu-Han, Tsai Tsung-Ting, Chen Chia-Ling, Shen Ting-Jing, Jhan Ming-Kai, Tseng Po-Chun, Lin Chiou-Feng
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Front Cell Infect Microbiol. 2020 Jul 28;10:375. doi: 10.3389/fcimb.2020.00375. eCollection 2020.
Aging and chronic condition increase the incidence of dengue virus (DENV) infection, generally through a mechanism involving immunosenescence; however, the alternative effects of cellular senescence, which alters cell susceptibility to viral infection, remain unknown. Human monocytic THP-1 cells (ATCC TIB-202) treated with D-galactose to induce cellular senescence were susceptible to DENV infection. These senescent cells showed increased viral entry/binding, gene/protein expression, and dsRNA replication. The use of a replicon system showed that pharmacologically induced senescence did not enhance the effects on viral protein translation. By examining viral receptor expression, we found increased expression of CD209 (DC-SIGN) in the senescent cells. Interleukin (IL)-10 was aberrantly produced at high levels by the senescent cells, and the expression of the DENV receptor DC-SIGN was increased in these senescent cells, partially via IL-10-mediated regulation of the JAK2-STAT3 signaling pathway. The results demonstrate that a senescent phenotype facilitates DENV infection, probably by increasing DC-SIGN expression.
衰老和慢性疾病通常通过涉及免疫衰老的机制增加登革病毒（DENV）感染的发生率；然而，细胞衰老改变细胞对病毒感染易感性的其他影响仍不清楚。用D-半乳糖处理以诱导细胞衰老的人单核细胞THP-1细胞（ATCC TIB-202）易受DENV感染。这些衰老细胞表现出病毒进入/结合、基因/蛋白质表达和双链RNA复制增加。使用复制子系统表明，药理学诱导的衰老并未增强对病毒蛋白质翻译的影响。通过检测病毒受体表达，我们发现衰老细胞中CD209（DC-SIGN）的表达增加。衰老细胞异常高水平产生白细胞介素（IL）-10，并且在这些衰老细胞中DENV受体DC-SIGN的表达增加，部分是通过IL-10介导的JAK2-STAT3信号通路调节。结果表明，衰老表型可能通过增加DC-SIGN表达促进DENV感染。
