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白细胞介素-10 通过抑制 MRC5 细胞中病毒诱导的自噬来阻断人巨细胞病毒的体外复制。

Interleukin-10 blocks in vitro replication of human cytomegalovirus by inhibiting the virus-induced autophagy in MRC5 cells.

机构信息

Department of Neonatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.

Department of Obstetrics, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China.

出版信息

Biochem Biophys Res Commun. 2014 Jun 13;448(4):448-53. doi: 10.1016/j.bbrc.2014.04.120. Epub 2014 May 2.

DOI:10.1016/j.bbrc.2014.04.120
PMID:24796673
Abstract

BACKGROUND

Interleukin-10 is an important cytokine that regulates immune response. Previous studies have shown that human cytomegalovirus can trigger cell autophagy during the early stages of infection. To our knowledge, whether IL-10 inhibits HCMV-induced autophagy and virus replication has not been studied previously.

OBJECTIVES

We investigated whether IL-10 affects cell viability and autophagy under the conditions of starvation and HCMV infection by using the MRC5 cell line. We also explored the role of IL-10-mediated autophagy on HCMV replication.

RESULTS

Our data showed that IL-10 inhibited the autophagic flux of the MRC5 cells irrespective of starvation or HCMV infection, and suppressed HCMV replication. The promotion of autophagy with either a pharmacological inducer (rapamycin), or a technique to over-express the BECN1 gene reversed the effect of IL-10 on virus replication. Furthermore, the PI3K/Akt signal pathway was activated when the cells were pretreated with IL-10.

CONCLUSIONS

Our results indicated that IL-10 can suppress HCMV replication by inhibiting autophagy in host cells during the early stages of infection.

摘要

背景

白细胞介素-10 是一种重要的细胞因子,可调节免疫反应。先前的研究表明,人类巨细胞病毒在感染早期可触发细胞自噬。据我们所知,白细胞介素-10 是否抑制 HCMV 诱导的自噬和病毒复制尚未被研究过。

目的

我们通过 MRC5 细胞系研究了白细胞介素-10 在饥饿和 HCMV 感染条件下对细胞活力和自噬的影响。我们还探讨了 IL-10 介导的自噬对 HCMV 复制的作用。

结果

我们的数据表明,白细胞介素-10 抑制了 MRC5 细胞的自噬通量,无论是否存在饥饿或 HCMV 感染,并且抑制了 HCMV 复制。用药理学诱导剂(雷帕霉素)或过表达 BECN1 基因的技术促进自噬,可逆转白细胞介素-10 对病毒复制的影响。此外,当细胞用白细胞介素-10 预处理时,PI3K/Akt 信号通路被激活。

结论

我们的结果表明,白细胞介素-10 可通过在感染早期抑制宿主细胞中的自噬来抑制 HCMV 的复制。

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