Pan Xiaohong, Xie Jiaxin, Zhang Zhidan, Guo Xiaomei, Li Jixiong, Lin Di, Qian Ying, Xu Jingwen, Hu Yunzhang, Shi Jiandong
Yunnan Provincial Key Laboratory of Vector-Borne Diseases Control and Research, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
National Kunming High-Level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China.
Virol J. 2025 Jul 14;22(1):239. doi: 10.1186/s12985-025-02803-w.
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.
1型单纯疱疹病毒（HSV-1）和2型单纯疱疹病毒（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仍不清楚。本研究对人包皮成纤维细胞（HFF-1）在HSV-1和HSV-2裂解感染期间进行了比较蛋白质组学分析，以阐明驱动不同毒力的宿主-病原体相互作用。使用数据非依赖采集质谱（DIA-MS），我们分别在HSV-1和HSV-2感染的细胞中鉴定出280和219种差异表达蛋白（DEP）。关键DEP显示出血清型特异性调节：HSV-1上调抗病毒效应因子（ISG20、IRF7），同时下调趋化因子信号（CXCL12、DEF8）并促进脂质代谢（PTDSS1）。相比之下，HSV-2上调炎症效应因子（IGHV3-9、SERPINA1），增强NF-κB信号（BCL3），并改变糖代谢（GYS1、FBN1）。通路富集分析表明，HSV-1抑制炎症和抗原呈递通路以逃避免疫反应，而HSV-2诱导更强的促炎反应以及与脂质和糖代谢相关的代谢重编程。总体而言，这些发现为理解血清型特异性发病机制提供了蛋白质组学路线图。
