High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/40438 |
Resumo: | Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention. |
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High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16HPV16 diversityIntralesionCervical cancerCiências Médicas::Medicina ClínicaScience & TechnologyInvasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention.Funded by Grants # 2011/24035-2 and # 2012/23290-1, São Paulo Research Foundation (FAPESP)ElsevierUniversidade do MinhoOliveira, Cristina Mendes deBravo, Ignacio G.Souza, Nathália Caroline Santiago eGenta, Maria Luiza Nogueira DiasFregnani, José Humberto Tavares GuerreiroTacla, MaricyCarvalho, Jesus PaulaLongatto Filho, AdhemarLevi, José Eduardo2015-082015-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/40438engde Oliveira, C. M., Bravo, I. G., Santiago e Souza, N. C., Nogueira Dias Genta, M. L., Tavares Guerreiro Fregnani, J. H., Tacla, M., . . . Levi, J. E. (2015). High-level of viral genomic diversity in cervical cancers: A Brazilian study on human papillomavirus type 16. Infection Genetics and Evolution, 34, 44-51. doi: 10.1016/j.meegid.2015.07.0021567-134810.1016/j.meegid.2015.07.00226160543http://www.sciencedirect.com/science/article/pii/S1567134815002646info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:22:44Zoai:repositorium.sdum.uminho.pt:1822/40438Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:16:17.044236Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 |
title |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 |
spellingShingle |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 Oliveira, Cristina Mendes de HPV16 diversity Intralesion Cervical cancer Ciências Médicas::Medicina Clínica Science & Technology |
title_short |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 |
title_full |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 |
title_fullStr |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 |
title_full_unstemmed |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 |
title_sort |
High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16 |
author |
Oliveira, Cristina Mendes de |
author_facet |
Oliveira, Cristina Mendes de Bravo, Ignacio G. Souza, Nathália Caroline Santiago e Genta, Maria Luiza Nogueira Dias Fregnani, José Humberto Tavares Guerreiro Tacla, Maricy Carvalho, Jesus Paula Longatto Filho, Adhemar Levi, José Eduardo |
author_role |
author |
author2 |
Bravo, Ignacio G. Souza, Nathália Caroline Santiago e Genta, Maria Luiza Nogueira Dias Fregnani, José Humberto Tavares Guerreiro Tacla, Maricy Carvalho, Jesus Paula Longatto Filho, Adhemar Levi, José Eduardo |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Oliveira, Cristina Mendes de Bravo, Ignacio G. Souza, Nathália Caroline Santiago e Genta, Maria Luiza Nogueira Dias Fregnani, José Humberto Tavares Guerreiro Tacla, Maricy Carvalho, Jesus Paula Longatto Filho, Adhemar Levi, José Eduardo |
dc.subject.por.fl_str_mv |
HPV16 diversity Intralesion Cervical cancer Ciências Médicas::Medicina Clínica Science & Technology |
topic |
HPV16 diversity Intralesion Cervical cancer Ciências Médicas::Medicina Clínica Science & Technology |
description |
Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-08 2015-08-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/40438 |
url |
http://hdl.handle.net/1822/40438 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
de Oliveira, C. M., Bravo, I. G., Santiago e Souza, N. C., Nogueira Dias Genta, M. L., Tavares Guerreiro Fregnani, J. H., Tacla, M., . . . Levi, J. E. (2015). High-level of viral genomic diversity in cervical cancers: A Brazilian study on human papillomavirus type 16. Infection Genetics and Evolution, 34, 44-51. doi: 10.1016/j.meegid.2015.07.002 1567-1348 10.1016/j.meegid.2015.07.002 26160543 http://www.sciencedirect.com/science/article/pii/S1567134815002646 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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