Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.

Human Papillomaviruses (HPV) cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to...

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Autores principales: Mandy Muller, Yves Jacob, Louis Jones, Amélie Weiss, Laurent Brino, Thibault Chantier, Vincent Lotteau, Michel Favre, Caroline Demeret
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:2be03d4cf36047a48fa4334873d83c722021-11-18T06:04:16ZLarge scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.1553-73661553-737410.1371/journal.ppat.1002761https://doaj.org/article/2be03d4cf36047a48fa4334873d83c722012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22761572/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Human Papillomaviruses (HPV) cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV). To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.Mandy MullerYves JacobLouis JonesAmélie WeissLaurent BrinoThibault ChantierVincent LotteauMichel FavreCaroline DemeretPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 6, p e1002761 (2012)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Mandy Muller
Yves Jacob
Louis Jones
Amélie Weiss
Laurent Brino
Thibault Chantier
Vincent Lotteau
Michel Favre
Caroline Demeret
Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.
description Human Papillomaviruses (HPV) cause widespread infections in humans, resulting in latent infections or diseases ranging from benign hyperplasia to cancers. HPV-induced pathologies result from complex interplays between viral proteins and the host proteome. Given the major public health concern due to HPV-associated cancers, most studies have focused on the early proteins expressed by HPV genotypes with high oncogenic potential (designated high-risk HPV or HR-HPV). To advance the global understanding of HPV pathogenesis, we mapped the virus/host interaction networks of the E2 regulatory protein from 12 genotypes representative of the range of HPV pathogenicity. Large-scale identification of E2-interaction partners was performed by yeast two-hybrid screenings of a HaCaT cDNA library. Based on a high-confidence scoring scheme, a subset of these partners was then validated for pair-wise interaction in mammalian cells with the whole range of the 12 E2 proteins, allowing a comparative interaction analysis. Hierarchical clustering of E2-host interaction profiles mostly recapitulated HPV phylogeny and provides clues to the involvement of E2 in HPV infection. A set of cellular proteins could thus be identified discriminating, among the mucosal HPV, E2 proteins of HR-HPV 16 or 18 from the non-oncogenic genital HPV. The study of the interaction networks revealed a preferential hijacking of highly connected cellular proteins and the targeting of several functional families. These include transcription regulation, regulation of apoptosis, RNA processing, ubiquitination and intracellular trafficking. The present work provides an overview of E2 biological functions across multiple HPV genotypes.
format article
author Mandy Muller
Yves Jacob
Louis Jones
Amélie Weiss
Laurent Brino
Thibault Chantier
Vincent Lotteau
Michel Favre
Caroline Demeret
author_facet Mandy Muller
Yves Jacob
Louis Jones
Amélie Weiss
Laurent Brino
Thibault Chantier
Vincent Lotteau
Michel Favre
Caroline Demeret
author_sort Mandy Muller
title Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.
title_short Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.
title_full Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.
title_fullStr Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.
title_full_unstemmed Large scale genotype comparison of human papillomavirus E2-host interaction networks provides new insights for e2 molecular functions.
title_sort large scale genotype comparison of human papillomavirus e2-host interaction networks provides new insights for e2 molecular functions.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/2be03d4cf36047a48fa4334873d83c72
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