title: Identification of human papillomavirus-16 E6 variation in cervical cancer and their impact on T and B cell epitopes.
abstract: The infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for development of cervical cancer. The intra-type variations of HPV have different biological and pathological consequences with respect to disease progression. In the present study, six major Indian variants were experimentally identified in E6 gene of HPV-16 and showed their impact on immunogenicity by in silico methods. Four different phylogenetic lineages were observed in sequences including European (E) prototype, European variant, Asian and American Asian variant classes and complete absence of African phylogenetic lineages. On the prediction of B- and T-cell epitopes, 18 and 23 potent epitopes for MHC-II alleles, 10 potent MHC-I and 15 B-cell epitopes in each reference and variant sequence were identified. Interestingly, the presence of variation H78Y and L83V result in creation of four new epitopes for the HLA-DQA1*0101/DQB1*0501. Out of 15 B-cell predicted epitopes, three most potent epitopes were identified in both reference and variant sequence. Notably the amino acid stretch from amino acid 16-60 and 76-94 are very important for the immunological properties of E6 protein because these regions contain majority of the predicted epitopes. In future, this could control the cervical cancer by targeting these amino acid stretches for the development of HPV-16 vaccine.
authors: Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, Uttar Pradesh, India; Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi (North Campus), New Delhi, India.
authors: Anoop
authors: A
authors: Kumar
authors: Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, Uttar Pradesh, India.
authors: Showket
authors: S
authors: Hussain
authors: School of Agricultural Biotechnology, Punjab Agricultural University, Ludhiana, Punjab, India.
authors: Inderjit Singh
authors: IS
authors: Yadav
authors: Division of Genome Modification and Carcinogenesis, German Cancer Center, DKFZ, Heidelberg, Germany.
authors: Lutz
authors: L
authors: Gissmann
authors: Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi (North Campus), New Delhi, India.
authors: K
authors: K
authors: Natarajan
authors: Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi (North Campus), New Delhi, India.
authors: Bhudev C
authors: BC
authors: Das
authors: Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), Noida, Uttar Pradesh, India. Electronic address: mausumi02@yahoo.com.
authors: Mausumi
authors: M
authors: Bharadwaj
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D018985:Epitopes, B-Lymphocyte / Q000235:genetics* / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D005260:Female; D059848:HLA-DQ alpha-Chains / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000276:immunology / Q000821:virology; D010802:Phylogeny; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D002583:Uterine Cervical Neoplasms / Q000821:virology
chemical_list: D004279:DNA, Viral; C068651:E6 protein, Human papillomavirus type 16; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins
keywords: Epitope; HPV; HPV variants; MHC alleles