Papillomavirus E5: the smallest oncoprotein with many functions

Venuti, Aldo; Paolini, Francesca; Nasir, Lubna; Corteggio, Annunziata; Roperto, Sante; Campo, M. Saveria; Borzacchiello, Giuseppe

doi:10.1186/1476-4598-10-140

Cited by 237 publications

(249 citation statements)

References 180 publications

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“…HPV presents well-known mechanisms to evade host immunity and delay its elimination, thus facilitating viral persistence [28]. When the virus is detected, an innate immune response occurs, and leads to the development of an adaptive immune response.…”

Section: Discussionmentioning

confidence: 99%

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

et al. 2016

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Aims: Human papillomavirus (HPV) is a known biologic carcinogen which is commonly transmitted through sexual intercourse. CD8 + T cells are known effectors against tumour cells and an important prognostic marker in HPV-induced cancers. COX-2 inhibitors enhance CD8 + T cell activity against some cancers. In this work, we sought to study the presence and activation of CD8 + T lymphocytes in lesions from K14-HPV16 transgenic mice and the immunomodulatory effect of celecoxib (CXB) over these cells.Main methods: Skin samples of CXB-treated and untreated HPV16 -/-and HPV16 +/-mice were enzymatically digested and analysed by flow cytometry to assess CD8 + and CD8 + CD107a + T cell infiltrates. Matched skin samples were classified histologically.Key findings: HPV16 +/-mice presented higher CD8 + T cell infiltration than HPV16 -/-animals (P 0.001). Older HPV16 +/-animals showed epidermal dysplasia and increased percentages of CD8 + CD107a + T cells compared with younger animals with hyperplasia (P 0.001), validating this model for testing the effects of celecoxib on CD8 + T cells. CXB-treated HPV16 +/-mice showed higher percentages of CD8 + CD107a + T cells compared with untreated HPV16 +/-animals (P 0.01), but no differences were observed concerning the progression of epidermal lesions.Significance: These findings indicate that celecoxib enhances the degranulation of CD8 + T cells on HPV16-induced lesions, suggesting the potential clinical use of COX-2 inhibitors. Additionally, this study demonstrates the usefulness of the K14-HPV16 mouse model for testing therapeutic immunomodulatory approaches.

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Section: Discussionmentioning

confidence: 99%

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

et al. 2016

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“…The role of E5 in HPV-induced carcinogenesis was reviewed by Maufort and coworkers in 2010 [36]. [37,38]. HPV has also evolved mechanisms to avoid the effects of type I interferon (IFN) which is produced by infected cells and has anti-viral, antiproliferative, anti-angiogenic and immune-stimulatory activities [37].…”

Section: Cell Transformation By Hpvsmentioning

confidence: 99%

“…E6 also down-regulates STAT-1 and reduces the binding of STAT-1 to IREs. E5 plays an important role in escape of both innate and cell-mediated immunity [38]. E5 protein also down-regulates MHC/HLA Class I but selectively only the surface expression of HLA-A and HLA-B which present viral peptides to MHC Class I-restricted cytotoxic T lymphocytes (CTLs), but not the natural killer (NK) cell inhibitory ligands HLA-C and HLA-E [38].…”

Section: Cell Transformation By Hpvsmentioning

confidence: 99%

“…E5 plays an important role in escape of both innate and cell-mediated immunity [38]. E5 protein also down-regulates MHC/HLA Class I but selectively only the surface expression of HLA-A and HLA-B which present viral peptides to MHC Class I-restricted cytotoxic T lymphocytes (CTLs), but not the natural killer (NK) cell inhibitory ligands HLA-C and HLA-E [38]. The bridging of innate and adaptive immune responses can be affected by E5 via the inhibition of CD1d-mediated cytokine production [38].…”

Section: Cell Transformation By Hpvsmentioning

confidence: 99%

“…E5 protein also down-regulates MHC/HLA Class I but selectively only the surface expression of HLA-A and HLA-B which present viral peptides to MHC Class I-restricted cytotoxic T lymphocytes (CTLs), but not the natural killer (NK) cell inhibitory ligands HLA-C and HLA-E [38]. The bridging of innate and adaptive immune responses can be affected by E5 via the inhibition of CD1d-mediated cytokine production [38]. In the future, potential new therapies of HPV infection could include not only the prevention of HPV entry into the cell but also interventions against HPV immune escape.…”

Section: Cell Transformation By Hpvsmentioning

confidence: 99%

See 2 more Smart Citations

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

Rautava

Syrjänen

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Viruses in colorectal cancer

Marongiu

Allgayer

2021

Molecular Oncology

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Increasing evidence suggests that microorganisms might represent at least highly interesting cofactors in colorectal cancer (CRC) oncogenesis and progression. Still, associated mechanisms, specifically in colonocytes and their microenvironmental interactions, are still poorly understood. Although, currently, at least seven viruses are being recognized as human carcinogens, only three of these – Epstein–Barr virus (EBV), human papillomavirus (HPV) and John Cunningham virus (JCV) – have been described, with varying levels of evidence, in CRC. In addition, cytomegalovirus (CMV) has been associated with CRC in some publications, albeit not being a fully acknowledged oncovirus. Moreover, recent microbiome studies set increasing grounds for new hypotheses on bacteriophages as interesting additional modulators in CRC carcinogenesis and progression. The present Review summarizes how particular groups of viruses, including bacteriophages, affect cells and the cellular and microbial microenvironment, thereby putatively contributing to foster CRC. This could be achieved, for example, by promoting several processes – such as DNA damage, chromosomal instability, or molecular aspects of cell proliferation, CRC progression and metastasis – not necessarily by direct infection of epithelial cells only, but also by interaction with the microenvironment of infected cells. In this context, there are striking common features of EBV, CMV, HPV and JCV that are able to promote oncogenesis, in terms of establishing latent infections and affecting p53‐/pRb‐driven, epithelial–mesenchymal transition (EMT)‐/EGFR‐associated and especially Wnt/β‐catenin‐driven pathways. We speculate that, at least in part, such viral impacts on particular pathways might be reflected in lasting (e.g. mutational or further genomic) fingerprints of viruses in cells. Also, the complex interplay between several species within the intestinal microbiome, involving a direct or indirect impact on colorectal and microenvironmental cells but also between, for example, phages and bacterial and viral pathogens, and further novel species certainly might, in part, explain ongoing difficulties to establish unequivocal monocausal links between specific viral infections and CRC.

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Papillomavirus E5: the smallest oncoprotein with many functions

Cited by 237 publications

References 180 publications

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

Celecoxib promotes degranulation of CD8+ T cells in HPV-induced lesions of K14-HPV16 transgenic mice

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

Viruses in colorectal cancer

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