ArticleJournal of virology2010
CD1d, a sentinel molecule bridging innate and adaptive immunity, is downregulated by the human papillomavirus (HPV) E5 protein: a possible mechanism for immune evasion by HPV.
Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 127 citations in OpenAlex.
- Role of E5 from HPV16 in the Evasion of the Immune Response.International journal of molecular sciences · 2026Review
- Advances in immunotherapy for HPV-associated malignancies: emerging strategies and clinical progress.Frontiers in immunology · 2026Review
- Molecular heterogeneity of HPV-associated cancers and strategies to overcome treatment resistance.Cancer heterogeneity and plasticity · 2026Article
- FOXP3-activated KCNMB2-AS1 promotes clear cell renal cell carcinoma through the miR-744-3p/CD1D axis.Cell division · 2025Article
- Review
- Virus-mediated immunosuppression in head and neck cancer.Oncogene · 2025Review
- Pre-invasive Lesion of Cervix Among Healthy and Immune Compromised Individuals Using Histopathological Examination: A Hospital Based Cross-Sectional Study.Journal of obstetrics and gynaecology of India · 2025Article
- E5 Oncoprotein: A Key Player in Human Papillomavirus-Positive Head and Neck Cancer Pathogenesis and Therapy Resistance.Viruses · 2025Review
- Sexually transmitted human papillomavirus and related sequelae.Clinical microbiology reviews · 2025Review
- Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use.Signal transduction and targeted therapy · 2025Review
- Research progress on tumor-infiltrating lymphocyte therapy for cervical cancer.Frontiers in immunology · 2025Review
- Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells.Clinical immunology (Orlando, Fla.) · 2024Review
- Identification and Functional Implications of the E5 Oncogene Polymorphisms of Human Papillomavirus Type 16.Tropical medicine and infectious disease · 2024Article
- The surveillance of viral infections by the unconventional Type I NKT cell.Frontiers in immunology · 2024Review
- Epidemiology, Molecular Pathogenesis, Immuno-Pathogenesis, Immune Escape Mechanisms and Vaccine Evaluation for HPV-Associated Carcinogenesis.Pathogens (Basel, Switzerland) · 2023Review
- CD1-mediated immune responses in mucosal tissues: molecular mechanisms underlying lipid antigen presentation system.Experimental & molecular medicine · 2023Review
- Carcinogenesis and management of human papillomavirus-associated cervical cancer.International journal of clinical oncology · 2023Review
- Immune responses in mildly versus critically ill COVID-19 patients.Frontiers in immunology · 2023Review
- Epigenetic control ofFrontiers in immunology · 2023Article
- Alteration of the IFN-Pathway by Human Papillomavirus Proteins: Antiviral Immune Response Evasion Mechanism.Biomedicines · 2022Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD1d and CD1d-restricted natural killer T (NKT) cells serve as a natural bridge between innate and adaptive immune responses to microbes. CD1d downregulation is utilized by a variety of microbes to evade immune detection. We demonstrate here that CD1d is downregulated in human papillomavirus (HPV)-positive cells in vivo and in vitro. CD1d immunoreactivity was strong in HPV-negative normal cervical epithelium but absent in HPV16-positive CIN1 and HPV6-positive condyloma lesions. We used two cell lines for in vitro assay; one was stably CD1d-transfected cells established from an HPV-negative cervical cancer cell line, C33A (C33A/CD1d), and the other was normal human vaginal keratinocyte bearing endogenous CD1d (Vag). Flow cytometry revealed that cell surface CD1d was downregulated in both C33A/CD1d and Vag cells stably transfected with HPV6 E5 and HPV16 E5. Although the steady-state levels of CD1d protein decreased in both E5-expressing cell lines compared to empty retrovirus-infected cells, CD1d mRNA levels were not affected. Confocal microscopy demonstrated that residual CD1d was not trafficked to the E5-expressing cell surface but colocalized with E5 near the endoplasmic reticulum (ER). In the ER, E5 interacted with calnexin, an ER chaperone known to mediate folding of CD1d. CD1d protein levels were rescued by the proteasome inhibitor, MG132, indicating a role for proteasome-mediated degradation in HPV-associated CD1d downregulation. Taken together, our data suggest that E5 targets CD1d to the cytosolic proteolytic pathway by inhibiting calnexin-related CD1d trafficking. Finally, CD1d-mediated production of interleukin-12 from the C33A/CD1d cells was abrogated in both E5-expressing cell lines. Decreased CD1d expression in the presence of HPV E5 may help HPV-infected cells evade protective immunological surveillance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.