The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion
Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide b...
| 發表在: | Frontiers in Cellular and Infection Microbiology |
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| Main Authors: | , , , , , , , , , , , , |
| 格式: | Article |
| 語言: | 英语 |
| 出版: |
Frontiers Media S.A.
2022-12-01
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| 主題: | |
| 在線閱讀: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.979800/full |
| _version_ | 1856968083516686336 |
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| author | Fernanda Silva Medeiros Mauro César da Silva Neila Caroline Henrique da Silva Thailany Thays Gomes Renan Garcia Gomes Larissa Albuquerque Paiva Fabiana Oliveira dos Santos Gomes Christina Alves Peixoto Maria Carolina Valença Rygaard Stefan Welkovic Maria Luiza Bezerra Menezes Eduardo Antônio Donadi Norma Lucena-Silva Norma Lucena-Silva |
| author_facet | Fernanda Silva Medeiros Mauro César da Silva Neila Caroline Henrique da Silva Thailany Thays Gomes Renan Garcia Gomes Larissa Albuquerque Paiva Fabiana Oliveira dos Santos Gomes Christina Alves Peixoto Maria Carolina Valença Rygaard Stefan Welkovic Maria Luiza Bezerra Menezes Eduardo Antônio Donadi Norma Lucena-Silva Norma Lucena-Silva |
| author_sort | Fernanda Silva Medeiros |
| collection | DOAJ |
| container_title | Frontiers in Cellular and Infection Microbiology |
| description | Human papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions. |
| format | Article |
| id | doaj-art-960a35c8403a4c4e9ff774ea85e8e2b8 |
| institution | Directory of Open Access Journals |
| issn | 2235-2988 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| spelling | doaj-art-960a35c8403a4c4e9ff774ea85e8e2b82025-08-19T20:01:27ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-12-011210.3389/fcimb.2022.979800979800The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesionFernanda Silva Medeiros0Mauro César da Silva1Neila Caroline Henrique da Silva2Thailany Thays Gomes3Renan Garcia Gomes4Larissa Albuquerque Paiva5Fabiana Oliveira dos Santos Gomes6Christina Alves Peixoto7Maria Carolina Valença Rygaard8Stefan Welkovic9Maria Luiza Bezerra Menezes10Eduardo Antônio Donadi11Norma Lucena-Silva12Norma Lucena-Silva13Laboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilLaboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilLaboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilLaboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilLaboratory of Molecular Biology, Institute of Integral Medicine Professor Fernando Figueira (IMIP) Hospital, Pediatric Oncology Service, Recife, BrazilGetúlio Vargas Hospital, Pernambuco Health Department, Recife, BrazilLaboratory of Ultrastructure, Department of Entomology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilLaboratory of Ultrastructure, Department of Entomology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilLaboratory of Molecular Biology, Institute of Integral Medicine Professor Fernando Figueira (IMIP) Hospital, Pediatric Oncology Service, Recife, BrazilIntegrated Health Center Amaury de Medeiros (CISAM), University of Pernambuco, Recife, BrazilIntegrated Health Center Amaury de Medeiros (CISAM), University of Pernambuco, Recife, BrazilClinical Immunology Division, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, BrazilLaboratory of Immunogenetics, Department of Immunology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, BrazilLaboratory of Molecular Biology, Institute of Integral Medicine Professor Fernando Figueira (IMIP) Hospital, Pediatric Oncology Service, Recife, BrazilHuman papillomavirus (HPV) is the major pathogen for cervical lesions. The evasion mechanism of the immune response and persistence of HPV infection can be influenced by polymorphisms (SNPs) in genes associated with transporter associated with antigen processing (TAP), which may change the peptide binding affinity or the TAP expression impacting the efficiency of peptide transport in the secretory pathway, and the presentation of peptides to cytotoxic T lymphocytes. This study aimed to evaluate the role of the TAP1 and TAP2 polymorphisms, TAP1, and TAP2 genes expressions, and protein levels in cervical cells presenting different degrees of pre-cancerous lesions in 296 immunocompetent women infected or not by HPV. TAP SNPs were genotyped by Sanger sequencing, and gene expression by real-time PCR. Aneuploidy was determined by DNA index using flow cytometry. TAP-1 and TAP-2 tissue expressions were evaluated by immunohistochemistry. The Asp697Gly SNP of TAP1 presented a risk for cellular aneuploidy (P=0.0244). HPV+ women had higher TAP-2 mRNA (P=0.0212) and protein (P<0.0001) levels. The TAP2D and TAP2E haplotypes were associated with the risk for aneuploidy and pre-cancerous lesions. In conclusion, nucleotide variability at the peptide binding region of peptide transporter genes, particularly of the TAP2 gene, may influence the HPV-peptide transportation from the cytosol to the endoplasmic reticulum, increasing the susceptibility to the development of high-grade cervical lesions.https://www.frontiersin.org/articles/10.3389/fcimb.2022.979800/fullTAP1TAP2HPVpolymorphismcervical lesion |
| spellingShingle | Fernanda Silva Medeiros Mauro César da Silva Neila Caroline Henrique da Silva Thailany Thays Gomes Renan Garcia Gomes Larissa Albuquerque Paiva Fabiana Oliveira dos Santos Gomes Christina Alves Peixoto Maria Carolina Valença Rygaard Stefan Welkovic Maria Luiza Bezerra Menezes Eduardo Antônio Donadi Norma Lucena-Silva Norma Lucena-Silva The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion TAP1 TAP2 HPV polymorphism cervical lesion |
| title | The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion |
| title_full | The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion |
| title_fullStr | The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion |
| title_full_unstemmed | The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion |
| title_short | The antigen processing-associated transporter gene polymorphism: Role on gene and protein expression in HPV-infected pre-cancerous cervical lesion |
| title_sort | antigen processing associated transporter gene polymorphism role on gene and protein expression in hpv infected pre cancerous cervical lesion |
| topic | TAP1 TAP2 HPV polymorphism cervical lesion |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.979800/full |
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