Identification of the impact on T- and B- cell epitopes of human papillomavirus type-16 E6 and E7 variant in Southwest China

Chenzhang, Yuwei; Wen, Qiang; Ding, Xianping; Cao, Man; Chen, Zuyi; Mu, Xuemei; Wang, Tao

doi:10.1016/j.imlet.2016.09.013

Cited by 10 publications

(10 citation statements)

References 34 publications

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“…The extent of evolutionary conservation level of an amino acid position is largely determined by its structural and functional importance. For the first time, it is informed that the amino acid mutation in E6 and E7 made different changes in the conservation of structural and functional residues compared to the reference sequence . For the secondary structural analysis, we found first that H85Y, E36Q, I34L, and D32E in E6 and R77C in E7 changed the secondary structure of the E6 and E7 proteins.…”

Section: Discussionmentioning

confidence: 91%

Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women

Zhao

Zhu

Guo

et al. 2019

Journal of Medical Virology

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Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high-grade squamous intraepithelial lesion (HSIL) group compared to the T," a potential binding site for TATA-binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1-3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 -related cervical lesions/cancer.

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Section: Discussionmentioning

confidence: 91%

Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women

Zhao

Zhu

Guo

et al. 2019

Journal of Medical Virology

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“…Ethnic variation in HLA allele frequencies among populations is an important factor to be considered while understanding vaccine-mediated immunity. There is an increased interest to develop human vaccines against important viral infections based on the HLA diversity of the particular population [ 24 ]. Vaccine against Hantavirus, an important etiological agent of HFRS has been reported [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Short peptide epitope design from hantaviruses causing HFRS

et al. 2017

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Several genotypes of the hantavirus cause hemorrhagic fever with renal syndrome (HFRS) and is an important public health problem worldwide. There is now growing interest to develop subunit vaccines especially focused to elicit cytotoxic T lymphocyte responses which are important against viral infection. We identified candidate T-cell epitopes that bind to Class I HLA supertypes towards identifying potential subunit vaccine entity. These epitopes are conserved in all 5 hantavirus genotypes of HFRS (Hantaan, Dobrava- Belgrade, Seoul, Gou virus and Amur). The epitopes identified from S and M segment genomes were analyzed for human proteasome cleavage, transporter associated antigen processing (TAP) efficiency and antigenicity using bioinformatic approaches. The epitope MRNTIMASK which had the two characteristics of high proteasomal cleavage score and TAP score, also had high antigenicity score. Our results indicate that this epitope from the nucleocapsid protein may be considered the most favorable moiety for the development of subunit peptide vaccine.

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“…Table 1 depicts the proteasome score, TAP score, MHC score, processing score, total score, and binding affinity of predicted epitopes for different alleles as determined using NetMHC ANN 3.4. According to the results, 17 out of 19 epitopes of E1 protein, such as ATDTGSDMV [40][41][42][43][44][45][46][47][48] [187][188][189][190][191][192][193][194][195] , were predicted to have binding affinity for MHC class I alleles. Among these, the CVSYWGVYY exhibited interactions with six alleles, viz, HLA-A*(29:02, 30:02, 11:01, 01:01, 68:01), and HLA-B*35: 01 (Table 1B).…”

Section: Cd8 + Ctl Epitopesmentioning

confidence: 99%

“…In addition, the CAVPVTTRY 4-12 epitope of E4 protein was predicted to have binding affinity for HLA-(A*29, A*30, B*58, B*35) allotypes (Table 1C). Among the five epitopes of E6 protein, RTEVYQFAF [41][42][43][44][45][46][47][48][49] and YSRIRE-LRY [72][73][74][75][76][77][78][79][80] were predicted to have binding affinity for HLA-A*(32:01, 29:02) and HLA-B*58: 01 MHC class I alleles (Table 1D). Out of 13 MHC-binding E7 peptides (Table 1E), STLSFVCPW [93][94][95][96][97][98][99][100][101] (HLA-A*32:01, HLA-B*58:01, HLA-B*57:01), LQQLFLSTL [87][88][89][90][91][92][93][94][95] (HLA-A*02:06), and QLFLSTLSF [89][90][91][92][93][94][95][96]…”

Section: Cd8 + Ctl Epitopesmentioning

confidence: 99%

“…36,37 Several studies reported that virtual peptides of HPV16 and 18 oncoproteins (E6 and E7) efficiently induce immune response in cervical cancer patients as revealed by their peripheral blood mononuclear cell samples. [38][39][40][41][42] However, cross-protection against all the hrHPV strains could not be ignored. 40 The cross-reactivity of CTL peptide is suspected to play an essential role in producing immune response against multiple strains.…”

Section: Introductionmentioning

confidence: 99%

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Designing of CD8+ and CD8+-overlapped CD4+ epitope vaccine by targeting late and early proteins of human papillomavirus

Kaliamurthi

Selvaraj

Kaushik

et al. 2018

BTT

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Background and aimHuman papillomavirus (HPV) is an oncogenic agent that causes over 90% of cases of cervical cancer in the world. Currently available prophylactic vaccines are type specific and have less therapeutic efficiency. Therefore, we aimed to predict the potential species-specific and therapeutic epitopes from the protein sequences of HPV45 by using different immunoinformatics tools.MethodsInitially, we determined the antigenic potential of late (L1 and L2) and early (E1, E2, E4, E5, E6, and E7) proteins. Then, major histocompatibility complex class I-restricted CD8+ T-cell epitopes were selected based on their immunogenicity. In addition, epitope conservancy, population coverage (PC), and target receptor-binding affinity of the immunogenic epitopes were determined. Moreover, we predicted the possible CD8+, nested interferon gamma (IFN-γ)-producing CD4+, and linear B-cell epitopes. Further, antigenicity, allergenicity, immunogenicity, and system biology-based virtual pathway associated with cervical cancer were predicted to confirm the therapeutic efficiency of overlapped epitopes.ResultsTwenty-seven immunogenic epitopes were found to exhibit cross-protection (≥55%) against the 15 high-risk HPV strains (16, 18, 31, 33, 35, 39, 51, 52, 56, 58, 59, 68, 69, 73, and 82). The highest PC was observed in Europe (96.30%), North America (93.98%), West Indies (90.34%), North Africa (90.14%), and East Asia (89.47%). Binding affinities of 79 docked complexes observed as global energy ranged from −10.80 to −86.71 kcal/mol. In addition, CD8+ epitope-overlapped segments in CD4+ and B-cell epitopes demonstrated that immunogenicity and IFN-γ-producing efficiency ranged from 0.0483 to 0.5941 and 0.046 to 18, respectively. Further, time core simulation revealed the overlapped epitopes involved in pRb, p53, COX-2, NF-X1, and HPV45 infection signaling pathways.ConclusionEven though the results of this study need to be confirmed by further experimental peptide sensitization studies, the findings on immunogenic and IFN-γ-producing CD8+ and overlapped epitopes provide new insights into HPV vaccine development.

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Identification of the impact on T- and B- cell epitopes of human papillomavirus type-16 E6 and E7 variant in Southwest China

Cited by 10 publications

References 34 publications

Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women

Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women

Short peptide epitope design from hantaviruses causing HFRS

Designing of CD8<sup>+</sup> and CD8<sup>+</sup>-overlapped CD4<sup>+</sup> epitope vaccine by targeting late and early proteins of human papillomavirus

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