Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblasts

Abstract 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 transc...

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Main Authors: Yu Zhang, Kalam Lo, Chunmei Wang, Guoliang Zhou, Xiping Feng, Jing Ni, Xi Chen
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Virology Journal
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Online Access:https://doi.org/10.1186/s12985-024-02595-5
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author Yu Zhang
Kalam Lo
Chunmei Wang
Guoliang Zhou
Xiping Feng
Jing Ni
Xi Chen
author_facet Yu Zhang
Kalam Lo
Chunmei Wang
Guoliang Zhou
Xiping Feng
Jing Ni
Xi Chen
author_sort Yu Zhang
collection DOAJ
description Abstract 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.
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spelling doaj-art-f31a2ef1a2a843d89db093a1ca5b89db2025-08-20T02:32:25ZengBMCVirology Journal1743-422X2024-12-0121111210.1186/s12985-024-02595-5Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblastsYu Zhang0Kalam Lo1Chunmei Wang2Guoliang Zhou3Xiping Feng4Jing Ni5Xi Chen6Department 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 StomatologyDepartment 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 StomatologyShanghai Veterinary Research Institute, Chinese Academy of Agricultural SciencesDancheng County Central HospitalDepartment 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 StomatologyDepartment of Periodontology, 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 StomatologyDepartment 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 StomatologyAbstract 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.https://doi.org/10.1186/s12985-024-02595-5Herpes simplex virusHuman gingival fibroblastsTranscriptomePeriodontitis
spellingShingle Yu Zhang
Kalam Lo
Chunmei Wang
Guoliang Zhou
Xiping Feng
Jing Ni
Xi Chen
Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblasts
Virology Journal
Herpes simplex virus
Human gingival fibroblasts
Transcriptome
Periodontitis
title Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblasts
title_full Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblasts
title_fullStr Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblasts
title_full_unstemmed Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblasts
title_short Herpes simplex virus-induced upregulation of inflammatory cytokines in human gingival fibroblasts
title_sort herpes simplex virus induced upregulation of inflammatory cytokines in human gingival fibroblasts
topic Herpes simplex virus
Human gingival fibroblasts
Transcriptome
Periodontitis
url https://doi.org/10.1186/s12985-024-02595-5
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AT guoliangzhou herpessimplexvirusinducedupregulationofinflammatorycytokinesinhumangingivalfibroblasts
AT xipingfeng herpessimplexvirusinducedupregulationofinflammatorycytokinesinhumangingivalfibroblasts
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