A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer

The Lancet ◽  
1996 ◽  
Vol 347 (9014) ◽  
pp. 1523-1527 ◽  
Author(s):  
L.K Borysiewicz ◽  
A Fiander ◽  
M Nimako ◽  
S Man ◽  
G.W.G Wilkinson ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Vaccinia Virus ◽  
Recombinant Vaccinia Virus ◽  
Recombinant Vaccinia ◽  
E6 And E7 ◽  
E7 Proteins

scholarly journals Endogenous Human Papillomavirus E6 and E7 Proteins Differentially Regulate Proliferation, Senescence, and Apoptosis in HeLa Cervical Carcinoma Cells

2003 ◽  
Vol 77 (2) ◽  
pp. 1551-1563 ◽  
Author(s):  
Rosa Anna DeFilippis ◽  
Edward C. Goodwin ◽  
Lingling Wu ◽  
Daniel DiMaio
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Cervical Carcinoma ◽  
Carcinoma Cells ◽  
Rb Pathway ◽  
Cervical Cancer Cells ◽  
E6 And E7 ◽  
E7 Proteins ◽  
E6 Protein

ABSTRACT Cervical cancer cells express high-risk human papillomavirus (HPV) E6 and E7 proteins, and repression of HPV gene expression causes the cells to cease proliferation and undergo senescence. However, it is not known whether both HPV proteins are required to maintain the proliferative state of cervical cancer cells, or whether mutations that accumulate during carcinogenesis eliminate the need for one or the other of them. To address these questions, we used the bovine papillomavirus E2 protein to repress the expression of either the E6 protein or the E7 protein encoded by integrated HPV18 DNA in HeLa cervical carcinoma cells. Repression of the E7 protein activated the Rb pathway but not the p53 pathway and triggered senescence, whereas repression of the E6 protein activated the p53 pathway but not the Rb pathway and triggered both senescence and apoptosis. Telomerase activity, cyclin-dependent kinase activity, and expression of c-myc were markedly inhibited by repression of either E6 or E7. These results demonstrate that continuous expression of both the E6 and the E7 protein is required for optimal proliferation of cervical carcinoma cells and that the two viral proteins exert distinct effects on cell survival and proliferation. Therefore, strategies that inhibit the expression or activity of either viral protein are likely to inhibit the growth of HPV-associated cancers.

Roles of E6 and E7 Human Papillomavirus Proteins in Molecular Pathogenesis of Cervical Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 926-934 ◽  
Author(s):  
Eskandar Taghizadeh ◽  
Sepideh Jahangiri ◽  
Daryoush Rostami ◽  
Forough Taheri ◽  
Pedram Ghorbani Renani ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Cellular Response ◽  
Therapeutic Strategies ◽  
Cellular Communication ◽  
Mtor Signaling Pathway ◽  
Health Concerns ◽  
E6 And E7 ◽  
E7 Proteins

Human papillomavirus (HPV) cancers are expected to be major global health concerns in the upcoming decades. The growth of HPV-positive cancer cells depends on the consistent expression of oncoprotein which has been poorly taken into account in the cellular communication. Among them, E6/E7 oncoproteins are attractive therapeutic targets as their inhibition rapidly leads to the onset of aging in HPV-positive cancer cells. This cellular response is associated with the regeneration of p53, pRb anti-proliferative proteins as well as the mTOR signaling pathway; hence, the identification of involved and application of E6/E7 inhibitors can lead to new therapeutic strategies. In the present review, we focused on the pathogenicity of E6/E7 Proteins of human papillomavirus and their roles associated with the cervical cancer.

scholarly journals A recombinant human papillomavirus (HPV) type 16 L1–vaccinia virus murine challenge model demonstrates cell-mediated immunity against HPV virus-like particles

1999 ◽  
Vol 80 (9) ◽  
pp. 2471-2475 ◽  
Author(s):  
Dianne Marais ◽  
Jo-Ann Passmore ◽  
James Maclean ◽  
Robert Rose ◽  
Anna-Lise Williamson
Keyword(s):  
Human Papillomavirus ◽  
Vaccinia Virus ◽  
Recombinant Vaccinia Virus ◽  
Cell Mediated Immunity ◽  
Hpv 16 ◽  
Recombinant Vaccinia ◽  
Virus Like Particles ◽  
Virus Challenge ◽  
Cell Mediated Immune Response ◽  
Prophylactic Vaccines

Human papillomavirus (HPV) virus-like particles (VLP) are emerging as the immunogen of choice for prophylactic vaccines. The inability to infect animals with HPV has prevented the testing of potential vaccines such as these in animal systems. This study describes the development of a recombinant vaccinia virus (VV)–HPV type 16 (HPV-16) VLP challenge model to evaluate the efficacy of the cell-mediated immune response following HPV-16 VLP immunization in mice. Inoculation of BALB/c and C57 BL/6 mice with HPV-16 VLP resulted in HPV VLP-specific T cell proliferative responses characterized by the production of both Th1 and Th2 cytokines, and afforded protection against virus challenge from recombinant VV expressing HPV-16 L1 (VVL1R-16). Protection was demonstrated by a 4·6 log10 reduction in ovarian titres of VVL1R-16 in vaccinated BALB/c mice and a 2·3 log10 reduction in vaccinated C57 BL/6 mice, compared with unvaccinated mice.

scholarly journals Selection of Indonesian Medicinal Plant Active Compounds as Inhibitor Candidates of Oncoproteins E6 and E7 Human Papillomavirus Type 16 by Molecular Docking

2021 ◽  
Vol 3 (1) ◽  
pp. 9-17
Author(s):  
Riyanti Weni Syafitri ◽  
Azzania Fibriani ◽  
Reza Aditama
Keyword(s):  
Cervical Cancer ◽  
Molecular Docking ◽  
Human Papillomavirus ◽  
Medicinal Plant ◽  
Binding Site ◽  
Active Compounds ◽  
Hpv 16 ◽  
E6 And E7 ◽  
E7 Proteins

Cervical cancer cases caused by infection with Human Papillomavirus (HPV), especially HPV 16 (60.5% of cases) continue to increase every year with a high mortality rate. The current anti-cancer drugs were not only specifically targeting cancer cells, but healthy cells and can cause serious side effects. Therefore, it is necessary to find safer alternative therapies, e.g., using active compounds from natural products. The purpose of this study was to find the active compounds of Indonesian medicinal plants potentially as an inhibitor of oncoprotein E6 and E7 HPV 16, the main protein causing cervical cancer by in silico method. In this study, 711 active compounds from 187 medicinal plant species were selected based on molecular weight, solubility, gastrointestinal absorption index, and drug-likeness. Compounds that meet the criteria were tested for their affinity and interaction profile with E6 and E7 proteins through the molecular docking method. The results of this study showed 164 compounds that met the criteria. The molecular docking analysis showed nine of the most potent compounds as E6 inhibitors on the E6AP binding site and six compounds on the p53 binding site. Besides that, there were eleven most potent compounds as E7 inhibitors.  The results of this study indicate that there are natural compounds that can inhibit E6 and E7 proteins and have further potential to be used as anti-HPV drugs. However, further research is needed to test these compounds in vitro and in vivo.

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