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Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny

Persistent infection with Human Papillomavirus (HPV) is responsible for almost all cases of cervical cancers, and HPV16 and HPV18 associated with the majority of these. These types differ in the proportion of viral minor nucleotide variants (MNVs) caused by APOBEC3 mutagenesis as well as integration...

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Autores principales: Løvestad, Alexander Hesselberg, Repesa, Adina, Costanzi, Jean-Marc, Lagström, Sonja, Christiansen, Irene Kraus, Rounge, Trine B., Ambur, Ole Herman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485212/
https://www.ncbi.nlm.nih.gov/pubmed/36100161
http://dx.doi.org/10.1016/j.tvr.2022.200247
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author Løvestad, Alexander Hesselberg
Repesa, Adina
Costanzi, Jean-Marc
Lagström, Sonja
Christiansen, Irene Kraus
Rounge, Trine B.
Ambur, Ole Herman
author_facet Løvestad, Alexander Hesselberg
Repesa, Adina
Costanzi, Jean-Marc
Lagström, Sonja
Christiansen, Irene Kraus
Rounge, Trine B.
Ambur, Ole Herman
author_sort Løvestad, Alexander Hesselberg
collection PubMed
description Persistent infection with Human Papillomavirus (HPV) is responsible for almost all cases of cervical cancers, and HPV16 and HPV18 associated with the majority of these. These types differ in the proportion of viral minor nucleotide variants (MNVs) caused by APOBEC3 mutagenesis as well as integration frequencies. Whether these traits extend to other types remains uncertain. This study aimed to investigate and compare genomic variability and chromosomal integration in the two phylogenetically distinct Alpha-7 and Alpha-9 clades of carcinogenic HPV types. The TaME-seq protocol was employed to sequence cervical cell samples positive for HPV31, HPV33 or HPV45 and combine these with data from a previous study on HPV16 and HPV18. APOBEC3 mutation signatures were found in Alpha-9 (HPV16/31/33) but not in Alpha-7 (HPV18/45). HPV45 had significantly more MNVs compared to the other types. Alpha-7 had higher integration frequency compared to Alpha-9. An increase in integration frequency with increased diagnostic severity was found for Alpha-7. The results highlight important differences and broaden our understanding of the molecular mechanisms behind cervical cancer induced by high-risk HPV types from the Alpha-7 and Alpha-9 clades.
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spelling pubmed-94852122022-09-21 Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny Løvestad, Alexander Hesselberg Repesa, Adina Costanzi, Jean-Marc Lagström, Sonja Christiansen, Irene Kraus Rounge, Trine B. Ambur, Ole Herman Tumour Virus Res Full Length Article Persistent infection with Human Papillomavirus (HPV) is responsible for almost all cases of cervical cancers, and HPV16 and HPV18 associated with the majority of these. These types differ in the proportion of viral minor nucleotide variants (MNVs) caused by APOBEC3 mutagenesis as well as integration frequencies. Whether these traits extend to other types remains uncertain. This study aimed to investigate and compare genomic variability and chromosomal integration in the two phylogenetically distinct Alpha-7 and Alpha-9 clades of carcinogenic HPV types. The TaME-seq protocol was employed to sequence cervical cell samples positive for HPV31, HPV33 or HPV45 and combine these with data from a previous study on HPV16 and HPV18. APOBEC3 mutation signatures were found in Alpha-9 (HPV16/31/33) but not in Alpha-7 (HPV18/45). HPV45 had significantly more MNVs compared to the other types. Alpha-7 had higher integration frequency compared to Alpha-9. An increase in integration frequency with increased diagnostic severity was found for Alpha-7. The results highlight important differences and broaden our understanding of the molecular mechanisms behind cervical cancer induced by high-risk HPV types from the Alpha-7 and Alpha-9 clades. Elsevier 2022-09-11 /pmc/articles/PMC9485212/ /pubmed/36100161 http://dx.doi.org/10.1016/j.tvr.2022.200247 Text en © 2022 Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Løvestad, Alexander Hesselberg
Repesa, Adina
Costanzi, Jean-Marc
Lagström, Sonja
Christiansen, Irene Kraus
Rounge, Trine B.
Ambur, Ole Herman
Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny
title Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny
title_full Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny
title_fullStr Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny
title_full_unstemmed Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny
title_short Differences in integration frequencies and APOBEC3 profiles of five high-risk HPV types adheres to phylogeny
title_sort differences in integration frequencies and apobec3 profiles of five high-risk hpv types adheres to phylogeny
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485212/
https://www.ncbi.nlm.nih.gov/pubmed/36100161
http://dx.doi.org/10.1016/j.tvr.2022.200247
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