CD11b 通过调节人神经母细胞瘤细胞的免疫反应来维持西尼罗河病毒的复制。

CD11b maintains West Nile virus replication through modulation of immune response in human neuroblastoma cells.

机构信息

Department of Microbiology, Shanghai Key Laboratory of Medical Biodefense, Faculty of Naval Medicine, Naval Medical University, 800 Xiang-Yin Road, Shanghai, 200433, China.

Center for Disease Control and Prevention of Southern Theater Command, Guangzhou, China.

出版信息

Virol J. 2024 Jul 14;21(1):158. doi: 10.1186/s12985-024-02427-6.

DOI:10.1186/s12985-024-02427-6

PMID:39004752

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11247799/

Abstract

BACKGROUND

West Nile virus (WNV) is a rapidly spreading mosquito-borne virus accounted for neuroinvasive diseases. An insight into WNV-host factors interaction is necessary for development of therapeutic approaches against WNV infection. CD11b has key biological functions and been identified as a therapeutic target for several human diseases. The purpose of this study was to determine whether CD11b was implicated in WNV infection.

METHODS

SH-SY5Y cells with and without MEK1/2 inhibitor U0126 or AKT inhibitor MK-2206 treatment were infected with WNV. CD11b mRNA levels were assessed by real-time PCR. WNV replication and expression of stress (ATF6 and CHOP), pro-inflammatory (TNF-α), and antiviral (IFN-α, IFN-β, and IFN-γ) factors were evaluated in WNV-infected SH-SY5Y cells with CD11b siRNA transfection. Cell viability was determined by MTS assay.

RESULTS

CD11b mRNA expression was remarkably up-regulated by WNV in a time-dependent manner. U0126 but not MK-2206 treatment reduced the CD11b induction by WNV. CD11b knockdown significantly decreased WNV replication and protected the infected cells. CD11b knockdown markedly increased TNF-α, IFN-α, IFN-β, and IFN-γ mRNA expression induced by WNV. ATF6 mRNA expression was reduced upon CD11b knockdown following WNV infection.

CONCLUSION

These results demonstrate that CD11b is involved in maintaining WNV replication and modulating inflammatory as well as antiviral immune response, highlighting the potential of CD11b as a target for therapeutics for WNV infection.

摘要

背景

西尼罗河病毒（WNV）是一种通过蚊子传播的快速传播的病毒，可导致神经侵入性疾病。深入了解WNV 与宿主因素的相互作用对于开发针对 WNV 感染的治疗方法是必要的。CD11b 具有关键的生物学功能，并已被确定为几种人类疾病的治疗靶点。本研究旨在确定 CD11b 是否与 WNV 感染有关。

方法

用或不用 MEK1/2 抑制剂 U0126 或 AKT 抑制剂 MK-2206 处理的 SH-SY5Y 细胞感染 WNV。通过实时 PCR 评估 CD11b mRNA 水平。用 CD11b siRNA 转染感染 WNV 的 SH-SY5Y 细胞，评估 WNV 复制和应激（ATF6 和 CHOP）、促炎（TNF-α）和抗病毒（IFN-α、IFN-β 和 IFN-γ）因子的表达。通过 MTS 测定法确定细胞活力。

结果

WNV 以时间依赖性方式显著上调 CD11b mRNA 表达。U0126 但不是 MK-2206 处理可降低 WNV 诱导的 CD11b 表达。CD11b 敲低显著降低 WNV 复制并保护感染细胞。CD11b 敲低显著增加 WNV 诱导的 TNF-α、IFN-α、IFN-β 和 IFN-γ mRNA 表达。CD11b 敲低后，WNV 感染时 ATF6 mRNA 表达减少。