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Role of the host restriction factor APOBEC3 on papillomavirus evolution
More than 270 different types of papillomaviruses have been discovered in a wide array of animal species. Despite the great diversity of papillomaviruses, little is known about the evolutionary processes that drive host tropism and the emergence of oncogenic genotypes. Although host defense mechanis...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999249/ https://www.ncbi.nlm.nih.gov/pubmed/27570633 http://dx.doi.org/10.1093/ve/vev015 |
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author | Warren, Cody J. Van Doorslaer, Koenraad Pandey, Ahwan Espinosa, Joaquin M. Pyeon, Dohun |
author_facet | Warren, Cody J. Van Doorslaer, Koenraad Pandey, Ahwan Espinosa, Joaquin M. Pyeon, Dohun |
author_sort | Warren, Cody J. |
collection | PubMed |
description | More than 270 different types of papillomaviruses have been discovered in a wide array of animal species. Despite the great diversity of papillomaviruses, little is known about the evolutionary processes that drive host tropism and the emergence of oncogenic genotypes. Although host defense mechanisms have evolved to interfere with various aspects of a virus life cycle, viruses have also coevolved copious strategies to avoid host antiviral restriction. Our and other studies have shown that the cytidine deaminase APOBEC3 family members edit HPV genomes and restrict virus infectivity. Thus, we hypothesized that host restriction by APOBEC3 served as selective pressure during papillomavirus evolution. To test this hypothesis, we analyzed the relative abundance of all dinucleotide sequences in full-length genomes of 274 papillomavirus types documented in the Papillomavirus Episteme database (PaVE). Here, we report that TC dinucleotides, the preferred target sequence of several human APOBEC3 proteins (hA3A, hA3B, hA3F, and hA3H), are highly depleted in papillomavirus genomes. Given that HPV infection is highly tissue-specific, the expression levels of APOBEC3 family members were analyzed. The basal expression levels of all APOBEC3 isoforms, excluding hA3B, are significantly higher in mucosal skin compared with cutaneous skin. Interestingly, we reveal that Alphapapillomaviruses (alpha-PVs), a majority of which infects anogenital mucosa, display the most dramatic reduction in TC dinucleotide content. Computer modeling and reconstruction of ancestral alpha-PV genomes suggest that TC depletion occurred after the alpha-PVs diverged from their most recent common ancestor. In addition, we found that TC depletion in alpha-PVs is greatly affected by protein coding potential. Taken together, our results suggest that PVs replicating in tissues with high APOBEC3 levels may have evolved to evade restriction by selecting for variants that contain reduced APOBEC3 target sites in their genomes. |
format | Online Article Text |
id | pubmed-4999249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49992492016-08-25 Role of the host restriction factor APOBEC3 on papillomavirus evolution Warren, Cody J. Van Doorslaer, Koenraad Pandey, Ahwan Espinosa, Joaquin M. Pyeon, Dohun Virus Evol Research Article More than 270 different types of papillomaviruses have been discovered in a wide array of animal species. Despite the great diversity of papillomaviruses, little is known about the evolutionary processes that drive host tropism and the emergence of oncogenic genotypes. Although host defense mechanisms have evolved to interfere with various aspects of a virus life cycle, viruses have also coevolved copious strategies to avoid host antiviral restriction. Our and other studies have shown that the cytidine deaminase APOBEC3 family members edit HPV genomes and restrict virus infectivity. Thus, we hypothesized that host restriction by APOBEC3 served as selective pressure during papillomavirus evolution. To test this hypothesis, we analyzed the relative abundance of all dinucleotide sequences in full-length genomes of 274 papillomavirus types documented in the Papillomavirus Episteme database (PaVE). Here, we report that TC dinucleotides, the preferred target sequence of several human APOBEC3 proteins (hA3A, hA3B, hA3F, and hA3H), are highly depleted in papillomavirus genomes. Given that HPV infection is highly tissue-specific, the expression levels of APOBEC3 family members were analyzed. The basal expression levels of all APOBEC3 isoforms, excluding hA3B, are significantly higher in mucosal skin compared with cutaneous skin. Interestingly, we reveal that Alphapapillomaviruses (alpha-PVs), a majority of which infects anogenital mucosa, display the most dramatic reduction in TC dinucleotide content. Computer modeling and reconstruction of ancestral alpha-PV genomes suggest that TC depletion occurred after the alpha-PVs diverged from their most recent common ancestor. In addition, we found that TC depletion in alpha-PVs is greatly affected by protein coding potential. Taken together, our results suggest that PVs replicating in tissues with high APOBEC3 levels may have evolved to evade restriction by selecting for variants that contain reduced APOBEC3 target sites in their genomes. Oxford University Press 2015-12-16 /pmc/articles/PMC4999249/ /pubmed/27570633 http://dx.doi.org/10.1093/ve/vev015 Text en © The Author 2015. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Article Warren, Cody J. Van Doorslaer, Koenraad Pandey, Ahwan Espinosa, Joaquin M. Pyeon, Dohun Role of the host restriction factor APOBEC3 on papillomavirus evolution |
title | Role of the host restriction factor APOBEC3 on papillomavirus evolution |
title_full | Role of the host restriction factor APOBEC3 on papillomavirus evolution |
title_fullStr | Role of the host restriction factor APOBEC3 on papillomavirus evolution |
title_full_unstemmed | Role of the host restriction factor APOBEC3 on papillomavirus evolution |
title_short | Role of the host restriction factor APOBEC3 on papillomavirus evolution |
title_sort | role of the host restriction factor apobec3 on papillomavirus evolution |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999249/ https://www.ncbi.nlm.nih.gov/pubmed/27570633 http://dx.doi.org/10.1093/ve/vev015 |
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