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Human Polyomaviruses and Papillomaviruses

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 February 2018) | Viewed by 66617

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Special Issue Editor

Faculty of Health Sciences, Institute of Medical Biology, University of Tromsø, NO-9037 Tromsø, Norway
Interests: polyomavirus; viral oncology; anti-viral therapy; replication; host interaction; DNA viruses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human polyomaviruses (HPyV) and papillomaviruses (HPV) are small, non-enveloped viruses with a dsDNA of approximately 5 kbp and 8 kbp, respectively. They belong to the families Polyomaviridae and Papillomaviridae, respectively. Their members can infect mammals and birds, and, recently, polyomavirus and papillomavirus DNA has been detected in reptiles and fish. About 100 different subtypes of HPV are known, while, presently, 14 different polyomaviruses have been isolated in humans. While several HPV subtypes are known to play a causal role in anogenital and oropharyngeal cancers, only one, HPyV, seems to be associated with malignancy. Merkel cell polyomavirus is present in about 80% of all Merkel cell carcinomas, an aggressive type of skin cancer. The incidences of Merkel cell carcinoma and HPV-associated oropharyngeal carcinoma cases are increasing. Vaccines against the most common high-risk HPVs are now available as a prophylactic treatment. Immunotherapy-based clinical trial with Merkel cell carcinoma patients have shown promising results; however, there is an urgent need for additional anti-HPV and anti-HPyV therapies.

This Special Issue on “Human Polyomaviruses and Papillomaviruses” focuses on the role of HPyV and HPV in disease, their life cycles, host–cell interaction, mechanisms of oncogenesis, and anti-viral therapies. Topics may also include epidemiology, structure, screening, disease management and other aspects of HPyV and HPV. This Special Issue will include original research and review papers.

Prof. Dr. Ugo Moens
Guest Editor

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Keywords

  • Oncogenesis
  • Replication
  • Host cell interaction
  • Structure
  • Anti-viral therapy
  • Cell tropism
  • Co-infection
  • Epidemiology
  • Diagnosis

Published Papers (12 papers)

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Editorial

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5 pages, 158 KiB  
Editorial
Human Polyomaviruses and Papillomaviruses
by Ugo Moens
Int. J. Mol. Sci. 2018, 19(8), 2360; https://doi.org/10.3390/ijms19082360 - 10 Aug 2018
Cited by 9 | Viewed by 2443
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)

Research

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17 pages, 8751 KiB  
Article
Protein Expression in Tonsillar and Base of Tongue Cancer and in Relation to Human Papillomavirus (HPV) and Clinical Outcome
by Torbjörn Ramqvist, Anders Näsman, Bo Franzén, Cinzia Bersani, Andrey Alexeyenko, Susanne Becker, Linnea Haeggblom, Aeneas Kolev, Tina Dalianis and Eva Munck-Wikland
Int. J. Mol. Sci. 2018, 19(4), 978; https://doi.org/10.3390/ijms19040978 - 25 Mar 2018
Cited by 12 | Viewed by 5257
Abstract
Human papillomavirus (HPV) is a major etiological factor for tonsillar and the base of tongue cancer (TSCC/BOTSCC). HPV-positive and HPV-negative TSCC/BOTSCC present major differences in mutations, mRNA expression and clinical outcome. Earlier protein studies on TSCC/BOTSCC have mainly analyzed individual proteins. Here, the [...] Read more.
Human papillomavirus (HPV) is a major etiological factor for tonsillar and the base of tongue cancer (TSCC/BOTSCC). HPV-positive and HPV-negative TSCC/BOTSCC present major differences in mutations, mRNA expression and clinical outcome. Earlier protein studies on TSCC/BOTSCC have mainly analyzed individual proteins. Here, the aim was to compare a larger set of cancer and immune related proteins in HPV-positive and HPV-negative TSCC/BOTSCC in relation to normal tissue, presence of HPV, and clinical outcome. Fresh frozen tissue from 42 HPV-positive and 17 HPV-negative TSCC/BOTSCC, and corresponding normal samples, were analyzed for expression of 167 proteins using two Olink multiplex immunoassays. Major differences in protein expression between TSCC/BOTSCC and normal tissue were identified, especially in chemo- and cytokines. Moreover, 34 proteins, mainly immunoregulatory proteins and chemokines, were differently expressed in HPV-positive vs HPV-negative TSCC/BOTSCC. Several proteins were potentially related to clinical outcome for HPV-positive or HPV-negative tumors. For HPV-positive tumors, these were mostly related to angiogenesis and hypoxia. Correlation with clinical outcome of one of these, VEGFA, was validated by immunohistochemistry. Differences in immune related proteins between HPV-positive and HPV-negative TSCC/BOTSCC reflect the stronger activity of the immune defense in the former. Angiogenesis related proteins might serve as potential targets for therapy in HPV-positive TSCC/BOTSCC. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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16 pages, 4040 KiB  
Article
Agnoprotein Is an Essential Egress Factor during BK Polyomavirus Infection
by Margarita-Maria Panou, Emma L. Prescott, Daniel L. Hurdiss, Gemma Swinscoe, Michael Hollinshead, Laura G. Caller, Ethan L. Morgan, Louisa Carlisle, Marietta Müller, Michelle Antoni, David Kealy, Neil A. Ranson, Colin M. Crump and Andrew Macdonald
Int. J. Mol. Sci. 2018, 19(3), 902; https://doi.org/10.3390/ijms19030902 - 19 Mar 2018
Cited by 22 | Viewed by 6305
Abstract
BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late [...] Read more.
BK polyomavirus (BKPyV; hereafter referred to as BK) causes a lifelong chronic infection and is associated with debilitating disease in kidney transplant recipients. Despite its importance, aspects of the virus life cycle remain poorly understood. In addition to the structural proteins, the late region of the BK genome encodes for an auxiliary protein called agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to virion infectivity. Here, we demonstrate an essential role for agnoprotein in BK virus release. Viruses lacking agnoprotein fail to release from host cells and do not propagate to wild-type levels. Despite this, agnoprotein is not essential for virion infectivity or morphogenesis. Instead, agnoprotein expression correlates with nuclear egress of BK virions. We demonstrate that the agnoprotein binding partner α-soluble N-ethylmaleimide sensitive fusion (NSF) attachment protein (α-SNAP) is necessary for BK virion release, and siRNA knockdown of α-SNAP prevents nuclear release of wild-type BK virions. These data highlight a novel role for agnoprotein and begin to reveal the mechanism by which polyomaviruses leave an infected cell. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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16 pages, 582 KiB  
Article
Detection of HPV16 in Esophageal Cancer in a High-Incidence Region of Malawi
by Anja Lidwina Geßner, Angelika Borkowetz, Michael Baier, Angela Göhlert, Torsten J. Wilhelm, Alexander Thumbs, Eric Borgstein, Lars Jansen, Katrin Beer, Henning Mothes and Matthias Dürst
Int. J. Mol. Sci. 2018, 19(2), 557; https://doi.org/10.3390/ijms19020557 - 12 Feb 2018
Cited by 13 | Viewed by 4459
Abstract
This study was designed to explore the role of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC). Fifty-five patients receiving diagnostic upper gastrointestinal endoscopy at Zomba Central Hospital or Queen Elizabeth Hospital in Blantyre (Malawi) in 2010, were included in our study. [...] Read more.
This study was designed to explore the role of human papillomavirus (HPV) in esophageal squamous cell carcinoma (ESCC). Fifty-five patients receiving diagnostic upper gastrointestinal endoscopy at Zomba Central Hospital or Queen Elizabeth Hospital in Blantyre (Malawi) in 2010, were included in our study. Formalin-fixed paraffin-embedded biopsies were collected for histopathological diagnosis. HPV DNA was detected using multiplex Quantitative PCR (qPCR) and in situ hybridization (ISH). p16INK4a staining served as a surrogate marker for HPV oncogene activity. Cell proliferation was determined by Ki-67 staining. Human immunodeficiency virus (HIV) status was evaluated by serology. Data on the consumption of alcohol and tobacco, and history of tuberculosis (TBC), oral thrush, and Herpes zoster, were obtained by questionnaire. Forty patients displayed ESCC, three displayed dysplastic epithelium, and 12 displayed normal epithelium. HPV16 was detected in six ESCC specimens and in one dysplastic lesion. Among HPV-positive patients, viral load varied from 0.001 to 2.5 copies per tumor cell. HPV DNA presence could not be confirmed by ISH. p16INK4a positivity correlated with the presence of HPV DNA (p = 0.03). Of particular note is that the Ki-67 proliferation index, in areas with diffuse nuclear or cytoplasmatic p16INK4a staining ≥50%, was significantly higher in HPV-positive tumors compared to the corresponding p16INK4a stained areas of HPV-negative tumors (p = 0.004). HPV infection in ESCC was not associated with the consumption of tobacco or alcohol, but there were significantly more patients drinking locally brewed alcohol among HPV-positive tumor patients compared to non-tumor patients (p = 0.02) and compared to HPV-negative tumor patients (p = 0.047). There was no association between HIV infection, history of TBC, Herpes zoster, oral thrush, or HPV infection, in ESCC patients. Our indirect evidence for viral oncogene activity is restricted to single tumor cell areas, indicative of the role of HPV16 in the development of ESCC. The inhomogeneous presence of the virus within the tumor is reminiscent of the “hit and run” mechanism discussed for β-HPV types, such as HPV38. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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12 pages, 238 KiB  
Article
Cigarette Smoking Promotes Infection of Cervical Cells by High-Risk Human Papillomaviruses, but not Subsequent E7 Oncoprotein Expression
by Kimon Chatzistamatiou, Theodoros Moysiadis, Dimos Vryzas, Ekaterini Chatzaki, Andreas M. Kaufmann, Isabel Koch, Erwin Soutschek, Oliver Boecher, Athena Tsertanidou, Nikolaos Maglaveras, Pidder Jansen-Duerr and Theodoros Agorastos
Int. J. Mol. Sci. 2018, 19(2), 422; https://doi.org/10.3390/ijms19020422 - 31 Jan 2018
Cited by 12 | Viewed by 4283
Abstract
Persistent cervical infection with high-risk human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. To assess the effect of smoking on [...] Read more.
Persistent cervical infection with high-risk human papillomaviruses (hrHPVs) is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. To assess the effect of smoking on high-risk (hr) HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping (MPG), and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR) for hrHPV positivity of smokers compared to non-smokers was 1.785 (95% confidence intervals (CI): 1.365–2.332, p < 0.001). The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
248 KiB  
Article
Coinfection with Epstein–Barr Virus (EBV), Human Papilloma Virus (HPV) and Polyoma BK Virus (BKPyV) in Laryngeal, Oropharyngeal and Oral Cavity Cancer
by Bartłomiej Drop, Małgorzata Strycharz-Dudziak, Ewa Kliszczewska and Małgorzata Polz-Dacewicz
Int. J. Mol. Sci. 2017, 18(12), 2752; https://doi.org/10.3390/ijms18122752 - 19 Dec 2017
Cited by 53 | Viewed by 5736
Abstract
Most research providing evidence for the role of oncogenic viruses in head and neck squamous cell carcinoma (SCC) development is focused on one type of virus without analyzing possible interactions between two or more types of viruses. The aim of this study was [...] Read more.
Most research providing evidence for the role of oncogenic viruses in head and neck squamous cell carcinoma (SCC) development is focused on one type of virus without analyzing possible interactions between two or more types of viruses. The aim of this study was to analyse the prevalence of co-infection with human papillomavirus (HPV), Epstein–Barr virus (EBV) and polyoma BK virus (BKPyV) in oral, oropharyngeal and laryngeal squamous cell carcinomas in Polish patients. The correlations between viral infection, SCC, demographic parameters, evidence of metastases and grading were also investigated. Fresh-frozen tumour tissue samples were collected from 146 patients with laryngeal, oropharyngeal and oral cancer. After DNA extraction, the DNA of the studied viruses was detected using polymerase chain rection (PCR) assay. Males (87.7%) with a history of smoking (70.6%) and alcohol abuse (59.6%) prevailed in the studied group. Histological type G2 was recognized in 64.4% cases. The patients were most frequently diagnosed with T2 stage (36.3%) and with N1 stage (45.8%). Infection with at least two viruses was detected in 56.2% of patients. In this group, co-infection with HPV/EBV was identified in 34.1% of cases, EBV/BKV in 23.2%, HPV/BKV in 22.0%, and HPV/EBV/BKV in 20.7%. No difference of multiple infection in different locations of cancer was observed. The prevalence of poorly differentiated tumours (G3) was more frequent in co-infection with all three viruses than EBV or BKV alone. A significant correlation was observed between tumour dimensions (T) and lymph-node involvement (N) in co-infected patients compared to single infection. Further studies are necessary to clarify whether co-infection plays an important role in the initiation and/or progression of oncogenic transformation of oral, oropharyngeal and laryngeal epithelial cells. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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1676 KiB  
Article
A Role of Sp1 Binding Motifs in Basal and Large T-Antigen-Induced Promoter Activities of Human Polyomavirus HPyV9 and Its Variant UF-1
by Ugo Moens, Xiaobo Song, Marijke Van Ghelue, John A. Lednicky and Bernhard Ehlers
Int. J. Mol. Sci. 2017, 18(11), 2414; https://doi.org/10.3390/ijms18112414 - 14 Nov 2017
Cited by 5 | Viewed by 3248
Abstract
Human polyomavirus 9 (HPyV9) was originally detected in the serum of a renal transplant patient. Seroepidemiological studies showed that ~20–50% of the human population have antibodies against this virus. HPyV9 has not yet been associated with any disease and little is known about [...] Read more.
Human polyomavirus 9 (HPyV9) was originally detected in the serum of a renal transplant patient. Seroepidemiological studies showed that ~20–50% of the human population have antibodies against this virus. HPyV9 has not yet been associated with any disease and little is known about the route of infection, transmission, host cell tropism, and genomic variability in circulating strains. Recently, the HPyV9 variant UF-1 with an eight base-pair deletion, a thirteen base-pair insertion and with point mutations, creating three putative Sp1 binding sites in the late promoter was isolated from an AIDS patient. Transient transfection studies with a luciferase reporter plasmid driven by HPyV9 or UF1 promoter demonstrated that UF1 early and late promoters were stronger than HPyV9 promoters in most cell lines, and that the UF1 late promoter was more potently activated by HPyV9 large T-antigen (LTAg). Mutation of two Sp1 motifs strongly reduced trans-activation of the late UF1 promoter by HPyV9 LTAg in HeLa cells. In conclusion, the mutations in the UF1 late promoter seem to strengthen its activity and its response to stimulation by HPyV9 LTAg in certain cells. It remains to be investigated whether these promoter changes have an influence on virus replication and affect the possible pathogenic properties of the virus. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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5981 KiB  
Article
Viral-Cellular DNA Junctions as Molecular Markers for Assessing Intra-Tumor Heterogeneity in Cervical Cancer and for the Detection of Circulating Tumor DNA
by Katrin Carow, Mandy Gölitz, Maria Wolf, Norman Häfner, Lars Jansen, Heike Hoyer, Elisabeth Schwarz, Ingo B. Runnebaum and Matthias Dürst
Int. J. Mol. Sci. 2017, 18(10), 2032; https://doi.org/10.3390/ijms18102032 - 22 Sep 2017
Cited by 25 | Viewed by 5259
Abstract
The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV) DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined [...] Read more.
The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV) DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity. Moreover, we assessed the potential of these fragments as molecular tumor markers and analyzed their suitability for the detection of circulating tumor DNA in sera of cervical cancer patients. For intra-tumor heterogeneity analyses tumors of 8 patients with up to 5 integration sites per tumor were included. Tumor islands were micro-dissected from cryosections of several tissue blocks representing different regions of the tumor. Each micro-dissected tumor area served as template for a single junction-specific PCR. For the detection of circulating tumor-DNA (ctDNA) junction-specific PCR-assays were applied to sera of 21 patients. Samples were collected preoperatively and during the course of disease. In 7 of 8 tumors the integration site(s) were shown to be homogenously distributed throughout different tumor regions. Only one tumor displayed intra-tumor heterogeneity. In 5 of 21 analyzed preoperative serum samples we specifically detected junction fragments. Junction-based detection of ctDNA was significantly associated with reduced recurrence-free survival. Our study provides evidence that HPV-DNA integration is as an early step in cervical carcinogenesis. Clonality with respect to HPV integration opens new perspectives for the application of viral-cellular junction sites as molecular biomarkers in a clinical setting such as disease monitoring. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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Review

Jump to: Editorial, Research

12 pages, 544 KiB  
Review
Human Papilloma Virus and Autophagy
by Domenico Mattoscio, Alessandro Medda and Susanna Chiocca
Int. J. Mol. Sci. 2018, 19(6), 1775; https://doi.org/10.3390/ijms19061775 - 15 Jun 2018
Cited by 64 | Viewed by 9444
Abstract
Human papilloma viruses (HPVs) are a group of double-stranded DNA viruses known to be the primary cause of cervical cancer. In addition, evidence has now established their role in non-melanoma skin cancers, head and neck cancer (HNC), and the development of other anogenital [...] Read more.
Human papilloma viruses (HPVs) are a group of double-stranded DNA viruses known to be the primary cause of cervical cancer. In addition, evidence has now established their role in non-melanoma skin cancers, head and neck cancer (HNC), and the development of other anogenital malignancies. The prevalence of HPV-related HNC, in particular oropharyngeal cancers, is rapidly increasing, foreseeing that HPV-positive oropharyngeal cancers will outnumber uterine cervical cancers in the next 15–20 years. Therefore, despite the successful advent of vaccines originally licensed for cervical cancer prevention, HPV burden is still very high, and a better understanding of HPV biology is urgently needed. Autophagy is the physiological cellular route that accounts for removal, degradation, and recycling of damaged organelles, proteins, and lipids in lysosomal vacuoles. In addition to this scavenger function, autophagy plays a fundamental role during viral infections and cancers and is, therefore, frequently exploited by viruses to their own benefit. Recently, a link between HPV and autophagy has clearly emerged, leading to the conceivable development of novel anti-viral strategies aimed at restraining HPV infectivity. Here, recent findings on how oncogenic HPV16 usurp autophagy are described, highlighting similarities and differences with mechanisms adopted by other oncoviruses. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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17 pages, 2217 KiB  
Review
Role of the DNA Damage Response in Human Papillomavirus RNA Splicing and Polyadenylation
by Kersti Nilsson, Chengjun Wu and Stefan Schwartz
Int. J. Mol. Sci. 2018, 19(6), 1735; https://doi.org/10.3390/ijms19061735 - 12 Jun 2018
Cited by 15 | Viewed by 5108
Abstract
Human papillomaviruses (HPVs) have evolved to use the DNA repair machinery to replicate its DNA genome in differentiated cells. HPV activates the DNA damage response (DDR) in infected cells. Cellular DDR factors are recruited to the HPV DNA genome and position the cellular [...] Read more.
Human papillomaviruses (HPVs) have evolved to use the DNA repair machinery to replicate its DNA genome in differentiated cells. HPV activates the DNA damage response (DDR) in infected cells. Cellular DDR factors are recruited to the HPV DNA genome and position the cellular DNA polymerase on the HPV DNA and progeny genomes are synthesized. Following HPV DNA replication, HPV late gene expression is activated. Recent research has shown that the DDR factors also interact with RNA binding proteins and affects RNA processing. DDR factors activated by DNA damage and that associate with HPV DNA can recruit splicing factors and RNA binding proteins to the HPV DNA and induce HPV late gene expression. This induction is the result of altered alternative polyadenylation and splicing of HPV messenger RNA (mRNA). HPV uses the DDR machinery to replicate its DNA genome and to activate HPV late gene expression at the level of RNA processing. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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27 pages, 1204 KiB  
Review
High-Risk Human Papillomaviral Oncogenes E6 and E7 Target Key Cellular Pathways to Achieve Oncogenesis
by Nicole S. L. Yeo-Teh, Yoshiaki Ito and Sudhakar Jha
Int. J. Mol. Sci. 2018, 19(6), 1706; https://doi.org/10.3390/ijms19061706 - 08 Jun 2018
Cited by 138 | Viewed by 9518
Abstract
Infection with high-risk human papillomavirus (HPV) has been linked to several human cancers, the most prominent of which is cervical cancer. The integration of the viral genome into the host genome is one of the manners in which the viral oncogenes E6 and [...] Read more.
Infection with high-risk human papillomavirus (HPV) has been linked to several human cancers, the most prominent of which is cervical cancer. The integration of the viral genome into the host genome is one of the manners in which the viral oncogenes E6 and E7 achieve persistent expression. The most well-studied cellular targets of the viral oncogenes E6 and E7 are p53 and pRb, respectively. However, recent research has demonstrated the ability of these two viral factors to target many more cellular factors, including proteins which regulate epigenetic marks and splicing changes in the cell. These have the ability to exert a global change, which eventually culminates to uncontrolled proliferation and carcinogenesis. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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24 pages, 3347 KiB  
Review
The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors: A Review of Preclinical and Clinical Studies
by Giovanni Barillari, Paolo Monini, Cecilia Sgadari and Barbara Ensoli
Int. J. Mol. Sci. 2018, 19(5), 1418; https://doi.org/10.3390/ijms19051418 - 09 May 2018
Cited by 14 | Viewed by 4758
Abstract
Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV) is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN). CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC), a leading cause of death worldwide. [...] Read more.
Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV) is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN). CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC), a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV), as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI) have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s) of its development. This article reviews published work concerning: (i) the role of HPV proteins (including HPV-E5, E6 and E7) and of matrix-metalloproteinases (MMPs) in CIN evolution into invasive CC; and (ii) the effect of HIV-PI on events leading to CIN progression such as basement membrane and extracellular matrix invasion by HPV-positive CIN cells and the formation of new blood vessels. Results from the reviewed literature indicate that CIN clinical progression can be monitored by evaluating the expression of MMPs and HPV proteins and they suggest the use of HIV-PI or their derivatives for the block of CIN evolution into CC in both HIV-infected and uninfected women. Full article
(This article belongs to the Special Issue Human Polyomaviruses and Papillomaviruses)
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