scholarly journals PENGEMBANGAN ANTIVIRUS HUMAN PAPILLOMA VIRUS BERBASIS MOLEKUL KECIL

2015 ◽  
Vol 37 (1) ◽  
pp. 58
Author(s):  
Dwi Wulandari ◽  
T. Mirawati Sudiro
Keyword(s):  
Life Cycle ◽  
Development Strategy ◽  
Viral Proteins ◽  
Hpv Infection ◽  
Host Proteins ◽  
Papilloma Virus ◽  
Screening Programs ◽  
Protein Functions ◽  
E6 And E7 ◽  
Inhibitor Interaction

AbstrakSekalipun telah ada program skrining deteksi dini infeksi HPV maupun kanker servis sertaadanya dua vaksin yang telah berlisensi, sekarang ini belum ada obat antivirus yang efektif.Prospek pengembangan molekul kecil inhibitor sebagai antivirus HPV sangat menjanjikan.Modulasi interaksi diantara protein-protein virus atau protein virus dengan protein hospesmenjadi strategi dalam upaya pengembangan molekul inhibitor sebagai antiviral HPV. Halini didukung oleh kemajuan pengetahuan mengenai fungsi protein HPV yang terlibat dalamsiklus hidupnya diantaranya yaitu protein E1, E2, E6 dan E7. Beberapa kandidat antivirustelah ditemukan dan masih dalam penelitian lebih lanjut untuk mendapatkan senyawa turunandengan aktivitas yang lebih tinggi diantaranya asam bifenil sulfonasetat (inhibitor ATPase E1).Indandione dan repaglinide (inhibitor interaksi E1-E2) dan senyawa-senyawa lainnya.AbstractEventhough there has been screening programs for HPV infection and cervical canceras well as the two vaccines that have been licensed, currently there is no effective cure forHPV. The prospects of the development of small molecule inhibitors as HPV antiviral is verypromising. Development strategy was based on the modulation of interactions between viralproteins or viral proteins with host proteins. This is supported by the advances in knowledgeabout HPV’s protein functions involved in their life cycle such as E1, E2, E6 and E7 proteins.Some antiviral molecule candidates have been found and need further studies to obtainderivatives with higher activity including acid biphenyl sulfonasetat (inhibitor ATPase E1),Indandione & repaglinide (inhibitor interaction E1-E2), etc.

A Comprehensive Review on Crosstalk of Human Papilloma Virus oncoproteins and developmental/self-renewal pathways during the pathogenesis of uterine cervical cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Afza Ahmad ◽  
Irfan Ahmad Ansari
Keyword(s):  
Cervical Cancer ◽  
Human Papilloma Virus ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Hpv Infection ◽  
Uterine Cervical Cancer ◽  
Self Renewal ◽  
Papilloma Virus ◽  
Mesenchymal Transition ◽  
E6 And E7

: Cervical cancer, a cancer arising from the uterine cervix has been regarded as the fourth most frequent gynecological malignancy among females worldwide. Epidemiological reports have shown that uterine cervical cancer is a global health issue among womens of specially developing countries and consequently creates an economic and medical burden in the society. The main causative agent of cervical carcinoma is high risk human papilloma virus (HPV 16 and HPV 18). Molecular studies have revealed the expression two viral genes E6 and E7 after HPV infection in the epithelial cells of cervix. These gene products are known to inactivate the major tumor suppressors, p53 and retinoblastoma protein (pRB), respectively. Moreover, the role of self-renewal pathways such as Hedgehog, Notch and Wnt has also been linked with drug resistance in cancer cells and epithelial mesenchymal transition during metastasis in pathogenesis of cervical cancer. Although, the mechanism of interaction of HPV E6 and E7 with each and every component of above described developmental pathways is not elucidated yet, but preliminary reports of their crosstalk have begun to emerge. Understanding the interplay between these oncoproteins and developmental/self-renewal pathways is highly important in terms of designing new and targeted therapeutic approach against cervical cancer. Hence, this review cynosure the carcinogenesis of HPV with the brief description of its virology and also establishes the crosstalk between oncoproteins E6 & E7 and Hedgehog, Notch and Wnt signaling pathway.

scholarly journals Novel Antigenic Targets of HPV Therapeutic Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1262
Author(s):  
Ditte Rahbæk Boilesen ◽  
Karen Nørgaard Nielsen ◽  
Peter Johannes Holst
Keyword(s):  
Cervical Cancer ◽  
Head And Neck ◽  
Cytotoxic T Cells ◽  
Expression Patterns ◽  
Hpv Infection ◽  
Therapeutic Vaccines ◽  
Screening Programs ◽  
Associated Lesions ◽  
E6 And E7 ◽  
Hpv Oncoproteins

Human papillomavirus (HPV) infection is the cause of the majority of cervical cancers and head and neck cancers worldwide. Although prophylactic vaccines and cervical cancer screening programs have shown efficacy in preventing HPV-associated cervical cancer, cervical cancer is still a major cause of morbidity and mortality, especially in third world countries. Furthermore, head and neck cancer cases caused by HPV infection and associated mortality are increasing. The need for better therapy is clear, and therapeutic vaccination generating cytotoxic T cells against HPV proteins is a promising strategy. This review covers the current scene of HPV therapeutic vaccines in clinical development and discusses relevant considerations for the design of future HPV therapeutic vaccines and clinical trials, such as HPV protein expression patterns, immunogenicity, and exhaustion in relation to the different stages and types of HPV-associated lesions and cancers. Ultimately, while the majority of the HPV therapeutic vaccines currently in clinical testing target the two HPV oncoproteins E6 and E7, we suggest that there is a need to include more HPV antigens in future HPV therapeutic vaccines to increase efficacy and find that especially E1 and E2 could be promising novel targets.

To the question about diagnostics, prevention and therapy of pathology of the cervix

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (5) ◽  
pp. 33-36 ◽  
Author(s):  
S O Dubrovina ◽  
O A Ardintseva ◽  
L V Krasilnikova ◽  
M V Varicheva ◽  
O A Afrikyan
Keyword(s):  
Cervical Cancer ◽  
Evidence Base ◽  
Hpv Infection ◽  
Inosine Pranobex ◽  
Stereochemical Structure ◽  
Papilloma Virus ◽  
Screening Programs ◽  
Dna And Rna ◽  
High Prevalence ◽  
Dual Action

The review analyzes the latest American clinical guidelines on the effectiveness of cervical cancer screening programs, as well as references on the use of the immunomodulator isoprinosine for the treatment of patients infected with the human papilloma virus (HPV). The high prevalence of HPV and its role in the development of cervical cancer are shown. Isoprinosine belongs to immunomodulators with antiviral activity. It inhibits the replication of viral DNA and RNA by binding to cell ribosomes and changing their stereochemical structure. HPV infection, especially in the early stages, may be successfully cured till the complete elimination of the virus. Inosine Pranobex (Izoprinozin) having dual action and the most abundant evidence base, may be recognized as the optimal treatment option.

scholarly journals Prediction of Human proteins having interactions with HPV16 proteins using virus and host sequence motifs.

2021 ◽  
Vol 2 (2) ◽  
pp. 107-126
Author(s):  
Rabbiah Manzoor Malik ◽  
Sahar Fazal ◽  
Syed Touqeer Abbas ◽  
Aamer Bhatti ◽  
Mukhtar Ullah ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hpv Infection ◽  
Cervical Region ◽  
Sequence Motifs ◽  
Host Proteins ◽  
Human Host ◽  
Linear Peptide ◽  
Peptide Motifs ◽  
Human Proteins ◽  
E6 And E7

Background: Human Papillomavirus (HPV) infection has been found to be the major cause of cancer of cervical region, in females.  Genome of HPV codes for 6 functional proteins E1, E2, E4, E5, E6 and E7. These proteins play different roles in development of HPV infection and its progression towards cervical cancer. The interactions of HPV proteins with human DNA and proteins occurs in the presence of short linear peptide motifs on these proteins, have similar sequence to those found on proteins in human cells. Methods: After identification of human motifs in HPV proteins, by use of ELM resource, their counter domains were found from PROSITE. The proteins of human proteome containing these counter domains were predicted as the proteins having possibility of interactions with HPV proteins.    Results: we predicted 9468 human proteins for having interactions with HPV proteins. Our predicted proteins were enriched with the host proteins having possibility of being interacted by HPV proteins. 10% of our predicted proteins were already reported to be affected by one or more HPV proteins. The list of predicated proteins can be utilized to find out the connectivity between the virus HPV and human host. It can also be used to determine the pathways involved in pathogenesis of HPV leading towards the cervical cancer Conclusion: The list of predicated proteins can be utilized to find out the connectivity between the virus HPV and human host. It can also be used to determine the pathways involved in pathogenesis of HPV leading towards the cervical cancer.

Human papillomavirus oncoproteins and post-translational modifications: generating multifunctional hubs for overriding cellular homeostasis

2020 ◽  
Vol 401 (5) ◽  
pp. 585-599 ◽  
Author(s):  
Om Basukala ◽  
Vanessa Sarabia-Vega ◽  
Lawrence Banks
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Life Cycle ◽  
Growth Control ◽  
Viral Proteins ◽  
Mechanisms Of Action ◽  
Human Papillomaviruses ◽  
Post Translational Modifications ◽  
E6 And E7 ◽  
Hpv Oncoproteins

AbstractHuman papillomaviruses (HPVs) are major human carcinogens, causing around 5% of all human cancers, with cervical cancer being the most important. These tumors are all driven by the two HPV oncoproteins E6 and E7. Whilst their mechanisms of action are becoming increasingly clear through their abilities to target essential cellular tumor suppressor and growth control pathways, the roles that post-translational modifications (PTMs) of E6 and E7 play in the regulation of these activities remain unclear. Here, we discuss the direct consequences of some of the most common PTMs of E6 and E7, and how this impacts upon the multi-functionality of these viral proteins, and thereby contribute to the viral life cycle and to the induction of malignancy. Furthermore, it is becoming increasingly clear that these modifications, may, in some cases, offer novel routes for therapeutic intervention in HPV-induced disease.

E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP)

2006 ◽  
Vol preprint (2007) ◽  
pp. 1
Author(s):  
Bahig Shehata ◽  
Kristen Otto ◽  
Steven Sobol ◽  
Christina Stockwell ◽  
Cora Foulks ◽  
...  
Keyword(s):  
Human Papilloma Virus ◽  
Aggressive Behavior ◽  
Laryngeal Papillomatosis ◽  
Papilloma Virus ◽  
Oncogene Expression ◽  
E6 And E7 ◽  
E7 Oncogene

Human Papillomavirus Selected Properties and Related Cervical Cancer Prevention Issues

2020 ◽  
Vol 26 (18) ◽  
pp. 2073-2086
Author(s):  
Saule Balmagambetova ◽  
Andrea Tinelli ◽  
Ospan A. Mynbaev ◽  
Arip Koyshybaev ◽  
Olzhas Urazayev ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Prevention ◽  
Screening Program ◽  
Hpv Infection ◽  
Cervical Cancer Prevention ◽  
Point Of View ◽  
Prevention Strategies ◽  
Middle Income ◽  
Screening Programs

High-risk human papillomavirus strains are widely known to be the causative agents responsible for cervical cancer development. Aggregated damage caused by papillomaviruses solely is estimated in at least 5% of all malignancies of the human body and 16% in cancers that affect the female genital area. Enhanced understanding of the complex issue on how the high extent of carcinogenicity is eventually formed due to the infection by the Papoviridae family would contribute to enhancing current prevention strategies not only towards cervical cancer, but also other HPV associated cancers. This review article is aimed at presenting the key points in two directions: the current cervical cancer prevention and related aspects of HPV behavior. Virtually all applied technologies related to HPV diagnostics and screening programs, such as HPV tests, colposcopy-based tests (VIA/VILI), conventional and liquid-based cytology, currently available are presented. Issues of availability, advantages, and drawbacks of the screening programs, as well as vaccination strategies, are also reviewed in the article based on the analyzed sources. The current point of view regarding HPV is discussed with emphasis on the most problematic aspect of the HPV family concerning the observed increasing number of highly carcinogenic types. Present trends in HPV infection diagnostics throughout the human fluids and tissues are also reported, including the latest novelties in this field, such as HPV assay/self-sample device combinations. Besides, a brief outline of the related prevention issues in Kazakhstan, the leading country of Central Asia, is presented. Kazakhstan, as one of the post-soviet middle-income countries, may serve as an example of the current situation in those terrains, concerning the implementation of globally accepted cervical cancer prevention strategies. Along with positive achievements, such as the development of a nationwide screening program, a range of drawbacks is also analyzed and discussed.

scholarly journals Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

2021 ◽  
Author(s):  
Haoru Dong ◽  
Xinhua Shu ◽  
Qiang Xu ◽  
Chen Zhu ◽  
Andreas M. Kaufmann ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Treatment Strategies ◽  
Hpv Infection ◽  
Immune Checkpoint Blockade ◽  
Current Status ◽  
Future Directions ◽  
Sequencing Technologies ◽  
E6 And E7 ◽  
The Continuum

AbstractHuman papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to 38%–80% of head and neck squamous cell carcinoma (HNSCC) in oropharyngeal location (OPSCC) and nearly all cervical cancers contain the HPV genome which is implicated in causing cancer through its oncoproteins E6 and E7. Given by the biologically distinct HPV-related OPSCC and a more favorable prognosis compared to HPV-negative tumors, clinical trials on de-escalation treatment strategies for these patients have been studied. It is therefore raised the questions for the patient stratification if treatment de-escalation is feasible. Moreover, understanding the crosstalk of HPV-mediated malignancy and immunity with clinical insights from the proportional response rate to immune checkpoint blockade treatments in patients with HNSCC is of importance to substantially improve the treatment efficacy. This review discusses the biology of HPV-related HNSCC as well as successful clinically findings with promising candidates in the pipeline for future directions. With the advent of various sequencing technologies, further biomolecules associated with HPV-related HNSCC progression are currently being identified to be used as potential biomarkers or targets for clinical decisions throughout the continuum of cancer care.

scholarly journals Potential Effects of Human Papillomavirus Type Substitution, Superinfection Exclusion and Latency on the Efficacy of the Current L1 Prophylactic Vaccines

Viruses ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 22
Author(s):  
Ian N. Hampson ◽  
Anthony W. Oliver ◽  
Lynne Hampson
Keyword(s):  
Life Cycle ◽  
High Risk ◽  
Outcome Data ◽  
Benign Lesions ◽  
Complex Dynamic ◽  
Papilloma Virus ◽  
Superinfection Exclusion ◽  
Different Types ◽  
Hpv Types ◽  
Type Substitution

There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called “latent” infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data.

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