ArticleScientific reports2015
In silico mechanistic analysis of IRF3 inactivation and high-risk HPV E6 species-dependent drug response.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Phenotypic effect of the mutations H78Y and L83V in the E6 protein of human papillomavirus.Archives of virology · 2025Article
- cGAS/STING signaling pathway in gynecological malignancies: From molecular mechanisms to therapeutic values.Frontiers in immunology · 2025Review
- Circulating HPV Tumor DNA and Molecular Residual Disease in HPV-Positive Oropharyngeal Cancers: A Scoping Review.Diagnostics (Basel, Switzerland) · 2024Article
- Loxapine inhibits replication of hepatitis A virus in vitro and in vivo by targeting viral protein 2C.PLoS pathogens · 2024Article
- Structure of the p53 degradation complex from HPV16.Nature communications · 2024Article
- Unveiling the multifaceted realm of human papillomavirus: a comprehensive exploration of biology, interactions, and advances in cancer management.Frontiers in immunology · 2024Review
- Rational strategies for enhancing mAb binding to SARS-CoV-2 variants through CDR diversification and antibody-escape prediction.Frontiers in immunology · 2023Article
- Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy.Frontiers in oncology · 2023Review
- Molecular dynamics of the ERRγ ligand-binding domain bound with agonist and inverse agonist.PloS one · 2023Article
- High-Risk Mucosal Human Papillomavirus 16 (HPV16) E6 Protein and Cutaneous HPV5 and HPV8 E6 Proteins Employ Distinct Strategies To Interfere with Interferon Regulatory Factor 3-Mediated Beta Interferon Expression.Journal of virology · 2022Article
- Unique Mode of Antiviral Action of a Marine Alkaloid against Ebola Virus and SARS-CoV-2.Viruses · 2022Article
- Human Papillomaviruses as Infectious Agents in Gynecological Cancers. Oncogenic Properties of Viral Proteins.International journal of molecular sciences · 2022Review
- SARS-CoV-2 pan-variant inhibitory peptides deter S1-ACE2 interaction and neutralize delta and omicron pseudoviruses.Computational and structural biotechnology journal · 2022Article
- Human Papillomavirus-Associated Head and Neck Cancers. Where are We Now? A Systematic Review.Cancer management and research · 2022Review
- Article
- In Silico Approaches: A Way to Unveil Novel Therapeutic Drugs for Cervical Cancer Management.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- PPI Modulators of E6 as Potential Targeted Therapeutics for Cervical Cancer: Progress and Challenges in Targeting E6.Molecules (Basel, Switzerland) · 2021Review
- Structure of High-Risk Papillomavirus 31 E6 Oncogenic Protein and Characterization of E6/E6AP/p53 Complex Formation.Journal of virology · 2020Article
- Subversion of Host Innate Immunity by Human Papillomavirus Oncoproteins.Pathogens (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The high-risk human papillomavirus E6 (hrHPV E6) protein has been widely studied due to its implication in cervical cancer. In response to viral threat, activated kinases phosphorylate the IRF3 autoinhibitory domain, inducing type1 interferon production. HPV circumvents the antiviral response through the possible E6 interaction with IRF3 and abrogates p53's apoptotic activity by recruiting E6-associated protein. However, the molecular mechanism of IRF3 inactivation by hrHPV E6 has not yet been delineated. Therefore, we explored this mechanism through in silico examination of protein-protein and protein-ligand docking, binding energy differences, and computational alanine mutagenesis. Our results suggested that the LxxLL motifs of IRF3 binds within the hydrophobic pocket of E6, precluding Ser-patch phosphorylation, necessary for IRF3 activation and interferon induction. This model was further supported by molecular dynamics simulation. Furthermore, protein-ligand docking and drug resistance modeling revealed that the polar patches in the pocket of E6, which are crucial for complex stability and ligand binding, are inconsistent among hrHPV species. Such variabilities pose a risk of treatment failure owing to point mutations that might render drugs ineffective, and allude to multi-drug therapy. Overall, this study reveals a novel perspective of innate immune suppression in HPV infections and suggests a plausible therapeutic intervention.
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