Zhang Yu, Lo Kalam, Wang Chunmei, Zhou Guoliang, Feng Xiping, Ni Jing, Chen Xi
Department of Preventive Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai, China.
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
Virol J. 2024 Dec 19;21(1):323. doi: 10.1186/s12985-024-02595-5.
Herpes simplex virus type 1 (HSV-1) is the leading pathogen in the maxillo-facial region, affecting millions of individuals worldwide. Its periodic reactivation aligns with the most common course pattern of periodontal disease. The present study used RNA sequencing to investigate the transcriptomes of human gingival fibroblasts (HGFs) following HSV-1 infection from the early to late stages (12-72 h). At the early stage of infection (12 h post-infection), the most upregulated genes were interferon (IFN) regulatory factor family members, toll-like receptor (TLR) family members, IFN-β1, interleukin (IL)-1, C-C motif ligands, chemokine (C-X-C motif) ligands (CXCLs), and tumor necrosis factor (TNF). The strongest differential expression was observed in TNF, nucleotide-binding oligomerization domain-like receptor (NLR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. At the late stage of infection, the most upregulated genes were CXCLs and ILs. The differentially expressed genes were divided into nine clusters, according to the time series expression trend. Next, the prominent activation of TLRs, retinoic acid-inducible gene I-like receptor signaling, NLRs, and downstream IFNAR-JAK-STAT signaling pathways were observed via a modified HSV-1 infection map. The HSV-1-induced upregulation of inflammatory cytokines in HGFs may drive inflammatory processes in periodontitis. The dynamic variations in mRNAs in HGFs from the early to late stages after HSV-1 infection can provide an analytical framework for determining the host anti-viral defense response to antagonize HSV-1 infection in periodontal tissues.
单纯疱疹病毒1型（HSV-1）是颌面部区域的主要病原体，影响着全球数百万人。其周期性再激活与牙周病最常见的病程模式一致。本研究采用RNA测序技术，对HSV-1感染后早期至晚期（12-72小时）的人牙龈成纤维细胞（HGFs）转录组进行研究。在感染早期（感染后12小时），上调最明显的基因是干扰素（IFN）调节因子家族成员、Toll样受体（TLR）家族成员、IFN-β1、白细胞介素（IL）-1、C-C基序配体、趋化因子（C-X-C基序）配体（CXCLs）和肿瘤坏死因子（TNF）。在TNF、核苷酸结合寡聚化结构域样受体（NLR）和活化B细胞核因子κB轻链增强子（NF-κB）信号通路中观察到最强的差异表达。在感染后期，上调最明显的基因是CXCLs和ILs。根据时间序列表达趋势，将差异表达基因分为9个簇。接下来，通过改良的HSV-1感染图谱观察到TLRs、视黄酸诱导基因I样受体信号、NLRs和下游IFNAR-JAK-STAT信号通路的显著激活。HSV-1诱导的HGFs中炎性细胞因子上调可能驱动牙周炎的炎症过程。HSV-1感染后早期至晚期HGFs中mRNA的动态变化可为确定宿主抗病毒防御反应以拮抗牙周组织中HSV-1感染提供分析框架。
