ArticlePLoS pathogens2013
Human papillomavirus (HPV) upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte's innate immune response.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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Who cites it
121 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systems analysis of the HPV-microbiome-biofilm triad.Frontiers in cellular and infection microbiology · 2026Pooled it
- Molecular insights and therapeutic innovations in low-risk human papillomavirus-associated cutaneous wart.Molecular biology reports · 2026Review
- MIR31HG Modulates IL-4 Secretion by Keratinocytes and M2-Like Macrophage Polarization to Promote Local Immunosuppression in Condyloma Acuminata.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2026Article
- Innate immune recognition and microenvironmental reprogramming in HPV-induced cervical cancer: from pattern recognition receptor activation to immune tolerance disruption.Frontiers in cellular and infection microbiology · 2026Review
- Targeting innate immunity to overcome immune evasion in HPV-associated cancers.Frontiers in cellular and infection microbiology · 2026Review
- Ubiquitination dynamics in human tumour viruses: Viral infection, oncogenesis and antiviral therapy.The FEBS journal · 2026Review
- Association of Toll-like receptor signaling molecule gene polymorphisms with risk of cervical lesions in HPV-infected women.BMC infectious diseases · 2025Article
- Human Papillomavirus Integration Induces Oncogenic Host Gene Fusions in Oropharyngeal Cancers.Cancer discovery · 2025Article
- The role of innate immunity triggered by HPV infection in promoting cervical lesions.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Pathological roles of ubiquitination and deubiquitination systems in sepsis-induced myocardial dysfunction.Biomolecules & biomedicine · 2025Review
- Review
- Navigating therapeutic strategies: HPV classification in head and neck cancer.British journal of cancer · 2024Review
- Identification of diagnostic markers for moyamoya disease by combining bulk RNA-sequencing analysis and machine learning.Scientific reports · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- The cutaneous beta human papillomavirus type 8 E6 protein induces CCL2 through the CEBPα/miR-203/p63 pathway to support an inflammatory microenvironment in epidermodysplasia verruciformis skin lesions.Frontiers in cellular and infection microbiology · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis.Pathogens (Basel, Switzerland) · 2023Review
- Inhibition of the Cellular Deubiquitinase UCHL1 Suppresses SARS-CoV-2 Replication.American journal of respiratory cell and molecular biology · 2023Article
- Lactobacillus gasseri LGV03 isolated from the cervico-vagina of HPV-cleared women modulates epithelial innate immune responses and suppresses the growth of HPV-positive human cervical cancer cells.Translational oncology · 2023Article
- Advancing Immunotherapies for HPV-Related Cancers: Exploring Novel Vaccine Strategies and the Influence of Tumor Microenvironment.Vaccines · 2023Review
61 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
Abstract
Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV) may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs) but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion of host immunity for sustained periods of time. To understand the mechanisms underlying hrHPV's capacity to evade immunity, we studied PRR signaling in non, newly, and persistently hrHPV-infected keratinocytes. We found that active infection with hrHPV hampered the relay of signals downstream of the PRRs to the nucleus, thereby affecting the production of type-I interferon and pro-inflammatory cytokines and chemokines. This suppression was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) in keratinocytes. UCHL1 accomplished this by inhibiting tumor necrosis factor receptor-associated factor 3 (TRAF3) K63 poly-ubiquitination which lead to lower levels of TRAF3 bound to TANK-binding kinase 1 and a reduced phosphorylation of interferon regulatory factor 3. Furthermore, UCHL1 mediated the degradation of the NF-kappa-B essential modulator with as result the suppression of p65 phosphorylation and canonical NF-κB signaling. We conclude that hrHPV exploits the cellular protein UCHL1 to evade host innate immunity by suppressing PRR-induced keratinocyte-mediated production of interferons, cytokines and chemokines, which normally results in the attraction and activation of an adaptive immune response. This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist.
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