scholarly journals Production of Human Papillomavirus Type 16 E7 Protein in Lactococcus lactis

2002 ◽  
Vol 68 (2) ◽  
pp. 917-922 ◽  
Author(s):  
L. G. Berm�dez-Humar�n ◽  
P. Langella ◽  
A. Miyoshi ◽  
A. Gruss ◽  
R. Tamez Guerra ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Lactococcus Lactis ◽  
Oral Vaccine ◽  
Staphylococcal Nuclease ◽  
Cytoplasmic Protein ◽  
Human Papillomavirus Type 16 ◽  
Intracellular Proteolysis ◽  
Screening Systems ◽  
Viral Screening

ABSTRACT The E7 protein of human papillomavirus type 16 was produced in Lactococcus lactis. Secretion allowed higher production yields than cytoplasmic production. In stationary phase, amounts of cytoplasmic E7 were reduced, while amounts of secreted E7 increased, suggesting a phase-dependent intracellular proteolysis. Fusion of E7 to the staphylococcal nuclease, a stable protein, resulted in a highly stable cytoplasmic protein. This work provides new candidates for development of viral screening systems and for oral vaccine against cervical cancer.

scholarly journals Multiple ASF/SF2 Sites in the Human Papillomavirus Type 16 (HPV-16) E4-Coding Region Promote Splicing to the Most Commonly Used 3′-Splice Site on the HPV-16 Genome

2010 ◽  
Vol 84 (16) ◽  
pp. 8219-8230 ◽  
Author(s):  
Monika Somberg ◽  
Stefan Schwartz
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Splice Site ◽  
Binding Sites ◽  
Mrna Levels ◽  
Coding Region ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
E6 And E7

ABSTRACT Our results presented here demonstrate that the most abundant human papillomavirus type 16 (HPV-16) mRNAs expressing the viral oncogenes E6 and E7 are regulated by cellular ASF/SF2, itself defined as a proto-oncogene and overexpressed in cervical cancer cells. We show that the most frequently used 3′-splice site on the HPV-16 genome, site SA3358, which is used to produce primarily E4, E6, and E7 mRNAs, is regulated by ASF/SF2. Splice site SA3358 is immediately followed by 15 potential binding sites for the splicing factor ASF/SF2. Recombinant ASF/SF2 binds to the cluster of ASF/SF2 sites. Mutational inactivation of all 15 sites abolished splicing to SA3358 and redirected splicing to the downstream-located, late 3′-splice site SA5639. Overexpression of a mutant ASF/SF2 protein that lacks the RS domain, also totally inhibited the usage of SA3358 and redirected splicing to the late 3′-splice site SA5639. The 15 ASF/SF2 binding sites could be replaced by an ASF/SF2-dependent, HIV-1-derived splicing enhancer named GAR. This enhancer was also inhibited by the mutant ASF/SF2 protein that lacks the RS domain. Finally, silencer RNA (siRNA)-mediated knockdown of ASF/SF2 caused a reduction in spliced HPV-16 mRNA levels. Taken together, our results demonstrate that the major HPV-16 3′-splice site SA3358 is dependent on ASF/SF2. SA3358 is used by the most abundantly expressed HPV-16 mRNAs, including those encoding E6 and E7. High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer.

scholarly journals Human papillomavirus type 16 genomic variation in women with subsequent in situ or invasive cervical cancer: prospective population-based study

2018 ◽  
Vol 119 (9) ◽  
pp. 1163-1168 ◽  
Author(s):  
Laila Sara Arroyo-Mühr ◽  
Camilla Lagheden ◽  
Emilie Hultin ◽  
Carina Eklund ◽  
Hans-Olov Adami ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Invasive Cervical Cancer ◽  
Population Based ◽  
Genomic Variation ◽  
Population Based Study ◽  
Human Papillomavirus Type 16

Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer

2004 ◽  
Vol 74 (1) ◽  
pp. 117-126 ◽  
Author(s):  
Maria Lina Tornesello ◽  
Maria Luisa Duraturo ◽  
Immacolata Salatiello ◽  
Luigi Buonaguro ◽  
Simona Losito ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Intraepithelial Neoplasia ◽  
Human Papillomavirus Type 16 ◽  
Italian Women

scholarly journals Immunoinformatics Study on Early 4 Protein of Human Papillomavirus Type 16 for Cervical Cancer Vaccine Peptide Candidate

2019 ◽  
Vol 4 (2) ◽  
pp. 252-262
Author(s):  
Yani Suryani ◽  
Opik Taupiqurrohman ◽  
Muhammad Yusuf ◽  
Toto Subroto ◽  
Sukma Nuswantara
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Amino Acid ◽  
Cancer Vaccine ◽  
Vaccine Candidate ◽  
Peptide Vaccine ◽  
Human Papillomavirus Type 16 ◽  
Cervical Cancer Vaccine ◽  
Peptide Candidate

 The aims of this study were to carry out testing of the early 4 protein of type 16 HPV through immunoinformatics meth-ods in an effort to get the peptide vaccine candidate for cervical cancer. The software used are IEDB-AR, CABSdock and Accelrys Discovery Study 4.5. Based on the analysis that sequence of ami-no acid lysine, leucine, leucine, glycine, serine, threonine, tryp-tophan, proline and threonine (KLLGSTWPT) and the sequence of amino acid tyrosine, tyrosine, valine, leucine, histidine, leucine, cysteine, leucine, alanine, alanine, threonine, lysine, tyrosine, pro-line and leucine (YYVLHLCLAATKYPL) are peptide vaccine can-didate for cervical cancer from the early 4 protein of HPV type 16 

scholarly journals Human Papillomavirus Type 16 E7 Peptide-Directed CD8+ T Cells from Patients with Cervical Cancer Are Cross-Reactive with the Coronavirus NS2 Protein

2003 ◽  
Vol 77 (9) ◽  
pp. 5464-5474 ◽  
Author(s):  
Katja Nilges ◽  
Hanni Höhn ◽  
Henryk Pilch ◽  
Claudia Neukirch ◽  
Kirsten Freitag ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Response ◽  
T Cells ◽  
Human Papillomavirus ◽  
T Cell ◽  
T Cell Responses ◽  
Cross Reactivity ◽  
Antiviral Immune Response ◽  
Human Papillomavirus Type 16 ◽  
Cell Responses

ABSTRACT Human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are required for cellular transformation and represent candidate targets for HPV-specific and major histocompatibility complex class I-restricted CD8+-T-cell responses in patients with cervical cancer. Recent evidence suggests that cross-reactivity represents the inherent nature of the T-cell repertoire. We identified HLA-A2 binding HPV16 E7 variant peptides from human, bacterial, or viral origin which are able to drive CD8+-T-cell responses directed against wild-type HPV16 E7 amino acid 11 to 19/20 (E711-19/20) epitope YMLDLQPET(T) in vitro. CD8+ T cells reacting to the HLA-A2-presented peptide from HPV16 E711-19(20) recognized also the HLA-A2 binding peptide TMLDIQPED (amino acids 52 to 60) from the human coronavirus OC43 NS2 gene product. Establishment of coronavirus NS2-specific, HLA-A2-restricted CD8+-T-cell clones and ex vivo analysis of HPV16 E7 specific T cells obtained by HLA-A2 tetramer-guided sorting from PBL or tumor-infiltrating lymphocytes obtained from patients with cervical cancer showed that cross-reactivity with HPV16 E711-19(20) and coronavirus NS252-60 represents a common feature of this antiviral immune response defined by cytokine production. Zero of 10 patients with carcinoma in situ neoplasia and 3 of 18 patients with cervical cancer showed ≥0.1% HPV16 E7-reactive T cells in CD8+ peripheral blood lymphocytes. In vivo priming with HPV16 was confirmed in patients with cervical cancer or preinvasive HPV16-positive lesions using HLA-A2 tetramer complexes loaded with the E6-derived epitope KLPQLCTEL. In contrast, we could not detect E6-reactive T cells in healthy individuals. These data imply that the measurement of the HPV16 E711-19(20) CD8+-T-cell response may reflect cross-reactivity with a common pathogen and that variant peptides may be employed to drive an effective cellular immune response against HPV.

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