Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins

ABSTRACT The beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, the beta-3 species appears to be more highly represented in the mucosal epithelia than in the skin. Functional studies have also highlighted that bet...

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Autores principales:	Lucia Minoni, Maria Carmen Romero-Medina, Assunta Venuti, Cécilia Sirand, Alexis Robitaille, Gennaro Altamura, Florence Le Calvez-Kelm, Daniele Viarisio, Katia Zanier, Martin Müller, Rosita Accardi, Massimo Tommasino
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	beta-3 and mucosal HPV types p53 and pRb regulated pathways keratinocyte immortalization Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7a63374f31e6440894ef84bd043f7cfa
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spelling	oai:doaj.org-article:7a63374f31e6440894ef84bd043f7cfa2021-11-15T15:30:51ZTransforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins10.1128/mSphere.00398-202379-5042https://doaj.org/article/7a63374f31e6440894ef84bd043f7cfa2020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00398-20https://doaj.org/toc/2379-5042ABSTRACT The beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, the beta-3 species appears to be more highly represented in the mucosal epithelia than in the skin. Functional studies have also highlighted that beta-3 HPV49 shares some functional similarities with mucosal high-risk (HR) HPV16. Here, we describe the characterization of the in vitro transforming properties of the entire beta-3 species, which includes three additional HPV types: HPV75, HPV76, and HPV115. HPV49, HPV75, and HPV76 E6 and E7 (E6/E7), but not HPV115 E6 and E7, efficiently inactivate the p53 and pRb pathways and immortalize or extend the life span of human foreskin keratinocytes (HFKs). As observed for HR HPV16, cell cycle deregulation mediated by beta-3 HPV E6/E7 expression leads to p16INK4a accumulation, whereas no p16INK4a was detected in beta-2 HPV38 E6/E7 HFKs. As shown for HPV49 E6, HPV75 and HPV76 E6s degrade p53 by an E6AP/proteasome-mediated mechanism. Comparative analysis of cellular gene expression patterns of HFKs containing E6 and E7 from HR HPV16, beta-3 HPV types, and beta-2 HPV38 further highlights the functional similarities of HR HPV16 and beta-3 HPV49, HPV75, and HPV76. The expression profiles of these four HPV HFKs show some similarities and diverge substantially from those of beta-3 HPV115 E6/E7 and beta-2 HPV38 E6/E7 HFKs. In summary, our data show that beta-3 HPV types share some mechanisms with HR HPV types and pave the way for additional studies aiming to evaluate their potential role in human pathologies. IMPORTANCE Human papillomaviruses are currently classified in different genera. Mucosal HPVs belonging to the alpha genus have been clearly associated with carcinogenesis of the mucosal epithelium at different sites. Beta HPV types have been classified as cutaneous. Although findings indicate that some beta HPVs from species 1 and 2 play a role, together with UV irradiation, in skin cancer, very little is known about the transforming properties of most of the beta HPVs. This report shows the transforming activity of E6 and E7 from beta-3 HPV types. Moreover, it highlights that beta-3 HPVs share some biological properties more extensively with mucosal high-risk HPV16 than with beta-2 HPV38. This report provides new paradigms for a better understanding of the biology of the different HPV types and their possible association with lesions at mucosal and/or cutaneous epithelia.Lucia MinoniMaria Carmen Romero-MedinaAssunta VenutiCécilia SirandAlexis RobitailleGennaro AltamuraFlorence Le Calvez-KelmDaniele ViarisioKatia ZanierMartin MüllerRosita AccardiMassimo TommasinoAmerican Society for Microbiologyarticlebeta-3 and mucosal HPV typesp53 and pRb regulated pathwayskeratinocyte immortalizationMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	beta-3 and mucosal HPV types p53 and pRb regulated pathways keratinocyte immortalization Microbiology QR1-502
spellingShingle	beta-3 and mucosal HPV types p53 and pRb regulated pathways keratinocyte immortalization Microbiology QR1-502 Lucia Minoni Maria Carmen Romero-Medina Assunta Venuti Cécilia Sirand Alexis Robitaille Gennaro Altamura Florence Le Calvez-Kelm Daniele Viarisio Katia Zanier Martin Müller Rosita Accardi Massimo Tommasino Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins
description	ABSTRACT The beta human papillomaviruses (HPVs) are subdivided into 5 species (beta-1 to beta-5), and they were first identified in the skin. However, the beta-3 species appears to be more highly represented in the mucosal epithelia than in the skin. Functional studies have also highlighted that beta-3 HPV49 shares some functional similarities with mucosal high-risk (HR) HPV16. Here, we describe the characterization of the in vitro transforming properties of the entire beta-3 species, which includes three additional HPV types: HPV75, HPV76, and HPV115. HPV49, HPV75, and HPV76 E6 and E7 (E6/E7), but not HPV115 E6 and E7, efficiently inactivate the p53 and pRb pathways and immortalize or extend the life span of human foreskin keratinocytes (HFKs). As observed for HR HPV16, cell cycle deregulation mediated by beta-3 HPV E6/E7 expression leads to p16INK4a accumulation, whereas no p16INK4a was detected in beta-2 HPV38 E6/E7 HFKs. As shown for HPV49 E6, HPV75 and HPV76 E6s degrade p53 by an E6AP/proteasome-mediated mechanism. Comparative analysis of cellular gene expression patterns of HFKs containing E6 and E7 from HR HPV16, beta-3 HPV types, and beta-2 HPV38 further highlights the functional similarities of HR HPV16 and beta-3 HPV49, HPV75, and HPV76. The expression profiles of these four HPV HFKs show some similarities and diverge substantially from those of beta-3 HPV115 E6/E7 and beta-2 HPV38 E6/E7 HFKs. In summary, our data show that beta-3 HPV types share some mechanisms with HR HPV types and pave the way for additional studies aiming to evaluate their potential role in human pathologies. IMPORTANCE Human papillomaviruses are currently classified in different genera. Mucosal HPVs belonging to the alpha genus have been clearly associated with carcinogenesis of the mucosal epithelium at different sites. Beta HPV types have been classified as cutaneous. Although findings indicate that some beta HPVs from species 1 and 2 play a role, together with UV irradiation, in skin cancer, very little is known about the transforming properties of most of the beta HPVs. This report shows the transforming activity of E6 and E7 from beta-3 HPV types. Moreover, it highlights that beta-3 HPVs share some biological properties more extensively with mucosal high-risk HPV16 than with beta-2 HPV38. This report provides new paradigms for a better understanding of the biology of the different HPV types and their possible association with lesions at mucosal and/or cutaneous epithelia.
format	article
author	Lucia Minoni Maria Carmen Romero-Medina Assunta Venuti Cécilia Sirand Alexis Robitaille Gennaro Altamura Florence Le Calvez-Kelm Daniele Viarisio Katia Zanier Martin Müller Rosita Accardi Massimo Tommasino
author_facet	Lucia Minoni Maria Carmen Romero-Medina Assunta Venuti Cécilia Sirand Alexis Robitaille Gennaro Altamura Florence Le Calvez-Kelm Daniele Viarisio Katia Zanier Martin Müller Rosita Accardi Massimo Tommasino
author_sort	Lucia Minoni
title	Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins
title_short	Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins
title_full	Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins
title_fullStr	Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins
title_full_unstemmed	Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins
title_sort	transforming properties of beta-3 human papillomavirus e6 and e7 proteins
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/7a63374f31e6440894ef84bd043f7cfa
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Transforming Properties of Beta-3 Human Papillomavirus E6 and E7 Proteins

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