Serotype-specific host proteome remodeling in human foreskin fibroblasts during lytic HSV-1 and HSV-2 infection.

IF 4 3区医学 Q2 VIROLOGY

Virology Journal Pub Date : 2025-07-14 DOI:10.1186/s12985-025-02803-w

Xiaohong Pan, Jiaxin Xie, Zhidan Zhang, Xiaomei Guo, Jixiong Li, Di Lin, Ying Qian, Jingwen Xu, Yunzhang Hu, Jiandong Shi

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引用次数: 0

Abstract

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) exhibit distinct clinical manifestations, yet the molecular basis of their serotype-specific pathogenicity remains unclear. This study presents a comparative proteomic analysis of human foreskin fibroblast (HFF-1) cells during lytic HSV-1 and HSV-2 infections to elucidate host-pathogen interactions driving differential virulence. Using data-independent acquisition mass spectrometry (DIA-MS), we identified 280 and 219 differentially expressed proteins (DEPs) in HSV-1- and HSV-2-infected cells, respectively. Key DEPs revealed serotype-specific modulation: HSV-1 upregulated antiviral effectors (ISG20, IRF7) while downregulating chemokine signaling (CXCL12, DEF8) and promoting lipid metabolism (PTDSS1). In contrast, HSV-2 upregulated inflammatory effectors (IGHV3-9, SERPINA1), enhanced NF-κB signaling (BCL3), and altered glycometabolism (GYS1, FBN1). Pathway enrichment analysis showed that HSV-1 suppressed inflammatory and antigen presentation pathways to evade immune responses, whereas HSV-2 induced stronger pro-inflammatory responses and metabolic reprogramming related to lipid and glycometabolism. Overall, these findings provide a proteomic roadmap for understanding serotype-specific pathogenesis.

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溶性HSV-1和HSV-2感染期间人包皮成纤维细胞血清型特异性宿主蛋白质组重塑

单纯疱疹病毒1型（HSV-1）和2型（HSV-2）表现出不同的临床表现，但其血清型特异性致病性的分子基础尚不清楚。本研究对人包皮成纤维细胞（HFF-1）在裂解型HSV-1和HSV-2感染过程中的蛋白质组学分析进行了比较，以阐明宿主-病原体相互作用驱动的不同毒力。利用数据独立采集质谱法（DIA-MS），我们分别在HSV-1和hsv -2感染的细胞中鉴定出280和219个差异表达蛋白（DEPs）。关键DEPs显示血清型特异性调节：HSV-1上调抗病毒效应（ISG20, IRF7），下调趋化因子信号（CXCL12, DEF8），促进脂质代谢（PTDSS1）。相反，HSV-2上调炎症效应物（IGHV3-9, SERPINA1），增强NF-κB信号（BCL3），改变糖代谢（GYS1, FBN1）。途径富集分析表明，HSV-1抑制炎症和抗原递呈途径以逃避免疫应答，而HSV-2诱导更强的促炎反应和与脂质和糖代谢相关的代谢重编程。总之，这些发现为了解血清型特异性发病机制提供了蛋白质组学路线图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virology Journal 医学-病毒学

CiteScore

7.40

自引率

2.10%

发文量

186

审稿时长

1 months

期刊介绍： Virology Journal is an open access, peer reviewed journal that considers articles on all aspects of virology, including research on the viruses of animals, plants and microbes. The journal welcomes basic research as well as pre-clinical and clinical studies of novel diagnostic tools, vaccines and anti-viral therapies. The Editorial policy of Virology Journal is to publish all research which is assessed by peer reviewers to be a coherent and sound addition to the scientific literature, and puts less emphasis on interest levels or perceived impact.