scholarly journals Whole Genomic Analysis and Comparison of Two Canine Papillomavirus Type 9 Strains in Malignant and Benign Skin Lesions

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 736
Author(s):  
Chia-Yu Chang ◽  
Nanako Yamashita-Kawanishi ◽  
Sonoka Tomizawa ◽  
I-Li Liu ◽  
Wei-Tao Chen ◽  
...  
Keyword(s):  
Animal Species ◽  
Reference Strain ◽  
Genomic Analysis ◽  
Skin Lesions ◽  
Human Papillomaviruses ◽  
Viral Oncoproteins ◽  
E2 Protein ◽  
Viral Plaque ◽  
Malignant Lesions ◽  
E6 And E7

Papillomaviruses (PVs) usually cause benign proliferative lesions in the stratified epithelium of various animal species. However, some high-risk types of PVs have been proven to lead to malignant transformations. In dogs, several canine papillomaviruses (CPVs) have been identified in malignant lesions and are suggested as one of the risk factors for the development of squamous cell carcinomas (SCCs). In the present study, the full genomes of two CPV9 strains from recurrent SCCs of Dog 1 and skin viral papilloma (viral plaque) of Dog 2 were sequenced. Alignment of the two CPV9 sequences with the genome of the reference CPV9 strain (accession no. JF800656.1) derived from a solitary pigmented plaque was performed. Compared with the reference strain, a 27 bp in-frame insertion in the E1 gene was identified in both CPV9 strains in this study. In comparison with the CPV9 strains derived from benign lesions, the CPV9 from the SCCs of Dog 1 exhibited a 328 bp deletion at the 3′ end of the E2 and spacer sequence, which encoded a truncated deduced E2 protein and a chimeric E8^E2 protein. However, there was no difference in the mRNA expression levels of viral oncoproteins of E6 and E7 between the two CPV9 cases, suggesting that the oncogenesis of CPV9 for malignant transformation might be different from that of human papillomaviruses. The roles of E2 and E8^E2 deleted CPV9 in the oncogenesis of benign and malignant lesions should be further investigated.

scholarly journals Human Papillomaviruses-Associated Cancers: An Update of Current Knowledge

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2234
Author(s):  
Ena Pešut ◽  
Anamaria Đukić ◽  
Lucija Lulić ◽  
Josipa Skelin ◽  
Ivana Šimić ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Cell Cycle Control ◽  
Human Papillomaviruses ◽  
Causative Role ◽  
Dna Viruses ◽  
Viral Oncoproteins ◽  
Control Networks ◽  
Malignant Lesions ◽  
E6 And E7 ◽  
Regulation Of Cell Cycle

Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and on-going research in Croatia.

scholarly journals Human papillomavirus type 38 E6 and E7 act as tumour promoters during chemically induced skin carcinogenesis

2013 ◽  
Vol 94 (4) ◽  
pp. 749-752 ◽  
Author(s):  
Daniele Viarisio ◽  
Karin Müller Decker ◽  
Birgit Aengeneyndt ◽  
Christa Flechtenmacher ◽  
Lutz Gissmann ◽  
...  
Keyword(s):  
Skin Lesions ◽  
Human Papillomaviruses ◽  
Skin Carcinogenesis ◽  
Non Melanoma Skin Cancer ◽  
Multi Stage ◽  
Chemically Induced ◽  
Contrast Exposure ◽  
Tumour Promoters ◽  
Hpv Types ◽  
E6 And E7

Many findings support a possible involvement of a subgroup of human papillomaviruses (HPVs), called cutaneous beta HPV types, in the development of non-melanoma skin cancer. The skin of transgenic (Tg) mice expressing viral oncoproteins E6 and E7 from different cutaneous beta HPV types, including HPV38, showed an increased susceptibility to UV-induced and/or chemically induced skin carcinogenesis compared with wild-type animals. In this study, we show that beta HPV38 E6 and E7 oncoproteins act as promoter and progression factors in multi-stage skin carcinogenesis, strongly cooperating with the initiator and DNA damage agent 7,12-dimethylbenz[a]anthracene. In contrast, exposure of HPV38 E6/E7 Tg mice to the promoter 12-O-tetradecanoylphorbol-13-acetate did not significantly result in the development of skin lesions. These findings further support the role of beta HPV types in skin carcinogenesis, providing additional insight into their precise contribution to the multi-step process.

scholarly journals NCoR1 Mediates Papillomavirus E8^E2C Transcriptional Repression

2010 ◽  
Vol 84 (9) ◽  
pp. 4451-4460 ◽  
Author(s):  
Maria L. C. Powell ◽  
Jennifer A. Smith ◽  
Mathew E. Sowa ◽  
J. Wade Harper ◽  
Thomas Iftner ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Human Papillomaviruses ◽  
Full Length ◽  
Open Reading Frame ◽  
Long Control Region ◽  
E2 Protein ◽  
Reading Frame ◽  
Alternatively Spliced ◽  
E6 And E7 ◽  
Sirna Knockdown

ABSTRACT The papillomavirus E2 open reading frame encodes the full-length E2 protein as well as an alternatively spliced product called E8^E2C. E8^E2C has been best studied for the high-risk human papillomaviruses, where it has been shown to regulate viral genome levels and, like the full-length E2 protein, to repress transcription from the viral promoter that directs the expression of the viral E6 and E7 oncogenes. The repression function of E8^E2C is dependent on the 12-amino-acid N-terminal sequence from the E8 open reading frame (ORF). In order to understand the mechanism by which E8^E2C mediates transcriptional repression, we performed an unbiased proteomic analysis from which we identified six h igh-confidence c andidate i nteracting p roteins (HCIPs) for E8^E2C; the top two are NCoR1 and TBLR1. We established an interaction of E8^E2C with an NCoR1/HDAC3 complex and demonstrated that this interaction requires the wild-type E8 open reading frame. Small interfering RNA (siRNA) knockdown studies demonstrated the involvement of NCoR1/HDAC3 in the E8^E2C-dependent repression of the viral long control region (LCR) promoter. Additional genetic work confirmed that the papillomavirus E2 and E8^E2C proteins repress transcription through distinct mechanisms.

scholarly journals Detection of Human Papillomaviruses (HPVs) by Immunohistochemistry (P16ink4a) In Verrucous Skin Lesions

2021 ◽  
pp. 57-68
Author(s):  
Shone Thomas Babu ◽  
Mary Lilly
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Skin Lesions ◽  
Hpv Infection ◽  
Squamous Cell Carcinomas ◽  
Human Papillomaviruses ◽  
Cervical Lesions ◽  
Malignant Lesions ◽  
P16 Expression

Even though the p16 marker allows us to distinguish between benign and malignant verrucous skin lesions, we are unable to determine the patient's Human Papillomaviruses (HPVs) status despite the existence of recognized histopathological features that indicate its presence like koilocytic change, since a proper correlation couldn’t be made between this feature and p16 expression. Even though PV type 16 and 18 are a risk factor for developments of anogenital skin lesion diffuse p16 expression cannot always be attributed to HPVs as there may be several other risk factors causing skin lesions, unlike in cervical lesions such as squamous cell carcinomas, many studies have established the role of oncogenic HPVs with its carcinogenesis. This marker cannot be used as a surrogate for detection of HPV infection. The present study was the expression of p16INK4A in histological sections of verrucous skin lesions. To compare the expression of p16INK4a in benign, premalignant and malignant lesions involving the  skin and  comparing the  pattern of expression of p16INK4a in skin lesions  by  immunohistochemistry  and correlating the results with certain histological parameters that might indicate HPV infection.

scholarly journals Development and validation of a multiplex qPCR assay for detection and relative quantification of HPV16 and HPV18 E6 and E7 oncogenes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexia Bordigoni ◽  
Anne Motte ◽  
Hervé Tissot-Dupont ◽  
Philippe Colson ◽  
Christelle Desnues
Keyword(s):  
Limit Of Detection ◽  
Quantitative Polymerase Chain Reaction ◽  
Human Papillomaviruses ◽  
Molecular Techniques ◽  
Clinical Samples ◽  
Gene Encoding ◽  
Hpv Dna ◽  
E6 And E7 ◽  
High Risk Hpv ◽  
Development And Validation

AbstractHuman papillomaviruses (HPV) play a key role in promoting human anogenital cancers. Current high-risk HPV screening or diagnosis tests involve cytological or molecular techniques mostly based on qualitative HPV DNA detection. Here, we describe the development of a rapid quantitative polymerase chain reaction (qPCR) detection test of HPV16 and HPV18 oncogenes (E6 and E7) normalized on human gene encoding GAPDH. Optimized qPCR parameters were defined, and analytical specificities were validated. The limit of detection was 101 for all genes tested. Assay performances were evaluated on clinical samples (n = 96). Concordance between the Xpert HPV assay and the triplex assay developed here was 93.44% for HPV16 and 73.58% for HPV18. HPV co-infections were detected in 15 samples. The systems developed in the present study can be used in complement to traditional HPV tests for specifically validating the presence of HPV16 and/or HPV18. It can also be used for the follow-up of patients with confirmed infection and at risk of developing lesions, through the quantification of E6 and E7 oncogene expression (mRNA) normalized on the GAPDH expression levels.

The biological properties of E6 and E7 oncoproteins from human papillomaviruses

Virus Genes ◽  
2009 ◽  
Vol 40 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Raffaella Ghittoni ◽  
Rosita Accardi ◽  
Uzma Hasan ◽  
Tarik Gheit ◽  
Bakary Sylla ◽  
...  
Keyword(s):  
Biological Properties ◽  
Human Papillomaviruses ◽  
E6 And E7 Oncoproteins ◽  
E6 And E7

scholarly journals Mucosal Human Papillomaviruses Encode Four Different E5 Proteins Whose Chemistry and Phylogeny Correlate with Malignant or Benign Growth

2004 ◽  
Vol 78 (24) ◽  
pp. 13613-13626 ◽  
Author(s):  
Ignacio G. Bravo ◽  
Ángel Alonso
Keyword(s):  
Human Papillomaviruses ◽  
Structural Proteins ◽  
Phylogenetic Study ◽  
Protein Divergence ◽  
Early Proteins ◽  
Differential Involvement ◽  
E6 And E7 ◽  
Different Characteristics ◽  
L1 And L2 ◽  
Transformation Processes

ABSTRACT We performed a phylogenetic study of the E2-L2 region of human mucosal papillomaviruses (PVs) and of the proteins therein encoded. Hitherto, proteins codified in this region were known as E5 proteins. We show that many of these proteins could be spurious translations, according to phylogenetic and chemical coherence criteria between similar protein sequences. We show that there are four separate families of E5 proteins, with different characteristics of phylogeny, chemistry, and rate of evolution. For the sake of clarity, we propose a change in the present nomenclature. E5α is present in groups A5, A6, A7, A9, and A11, PVs highly associated with malignant carcinomas of the cervix and penis. E5β is present in groups A2, A3, A4, and A12, i.e., viruses associated with certain warts. E5γ is present in group A10, and E5δ is encoded in groups A1, A8, and A10, which are associated with benign transformations. The phylogenetic relationships between mucosal human PVs are the same when considering the oncoproteins E6 and E7 and the E5 proteins and differ from the phylogeny estimated for the structural proteins L1 and L2. Besides, the protein divergence rate is higher in early proteins than in late proteins, increasing in the order L1 < L2 < E6 ≈ E7 < E5. Moreover, the same proteins have diverged more rapidly in viruses associated with malignant transformations than in viruses associated with benign transformations. The E5 proteins display, therefore, evolutionary characteristics similar to those of the E6 and E7 oncoproteins. This could reflect a differential involvement of the E5 types in the transformation processes.

scholarly journals Antibodies against Early Proteins of Human Papillomaviruses as Diagnostic Markers for Invasive Cervical Cancer

1998 ◽  
Vol 36 (2) ◽  
pp. 475-480 ◽  
Author(s):  
Wolfgang Meschede ◽  
Klaus Zumbach ◽  
Joris Braspenning ◽  
Martin Scheffner ◽  
Luis Benitez-Bribiesca ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Human Papillomaviruses ◽  
Antibody Detection ◽  
Diagnostic Tools ◽  
Immunological Monitoring ◽  
Hpv Dna ◽  
Native Proteins ◽  
Human Sera ◽  
E6 And E7

Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among females worldwide. Specific human papillomaviruses (HPVs) and, most notably, HPV types 16 and 18 are recognized as being causally associated with this malignancy. Antibodies against early HPV proteins E6 and E7 have been found more often in patients with tumors than in controls. Existing peptide enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-E6 and anti-E7 antibodies in human sera have low levels of sensitivity and specificity and thus are not suitable for use as diagnostic tools. Based on highly purified recombinant native proteins, we developed four sandwich ELISAs for the detection of antibodies against HPV type 16 and 18 E6 and E7 proteins. We demonstrate their sensitivities and high degrees of specificity for cervical cancer. Among a total of 501 serum specimens from unselected patients with invasive cervical cancer, 52.9% reacted positively in at least one of the four assays. In contrast, among 244 serum specimens from control subjects without cervical cancer, only 2 reactive serum specimens (0.8%) were found. For 19 of 19 antibody-positive patients, the HPV type indicated by seroreactivity was identical to the HPV DNA type found in the tumor, which also indicates a high degree of specificity for antibody detection with respect to HPV type. In a direct comparison of 72 serum specimens from patients with cervical cancer, 56% of the specimens reacted in at least one of the four protein ELISAs, whereas 40% reacted in at least one of seven peptide ELISAs covering the four antigens. These assays could be of value for the detection of invasive cervical cancer in settings in which cytology-based early tumor screening is not available, for the clinical management of patients diagnosed with cervical cancer, and for the immunological monitoring of E6 and E7 vaccination trials.

Sign in / Sign up

Export Citation Format

Share Document