Chemistry (all); Biochemistry, Genetics and Molecular Biology (all); Physics and Astronomy (all); General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry
Abstract :
[en] Despite the high prevalence of both cervico-vaginal human papillomavirus (HPV) infection and bacterial vaginosis (BV) worldwide, their causal relationship remains unclear. While BV has been presumed to be a risk factor for HPV acquisition and related carcinogenesis for a long time, here, supported by both a large retrospective follow-up study (n = 6,085) and extensive in vivo data using the K14-HPV16 transgenic mouse model, we report a novel blueprint in which the opposite association also exists. Mechanistically, by interacting with several core members (NEMO, CK1 and β-TrCP) of both NF-κB and Wnt/β-catenin signaling pathways, we show that HPV E7 oncoprotein greatly inhibits host defense peptide expression. Physiologically secreted by the squamous mucosa lining the lower female genital tract, we demonstrate that some of these latter are fundamental factors governing host-microbial interactions. More specifically, several innate molecules down-regulated in case of HPV infection are hydrolyzed, internalized and used by the predominant Lactobacillus species as amino acid source sustaining their growth/survival. Collectively, this study reveals a new viral immune evasion strategy which, by its persistent/negative impact on lactic acid bacteria, ultimately causes the dysbiosis of vaginal microbiota.
Disciplines :
Microbiology
Author, co-author :
Lebeau, Alizée ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire
Bruyère, Diane ✱; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
RONCARATI, Patrick ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques
Peixoto, Paul ; INSERM, EFS BFC, UMR 1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté, Besançon, France ; EPIGENEXP platform, University of Bourgogne Franche-Comté, Besançon, France
Hervouet, Eric ; INSERM, EFS BFC, UMR 1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University of Bourgogne Franche-Comté, Besançon, France ; EPIGENEXP platform, University of Bourgogne Franche-Comté, Besançon, France
COBRAIVILLE, Gaël ; Centre Hospitalier Universitaire de Liège - CHU > > Service de rhumatologie
Taminiau, Bernard ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Masson, Murielle ; Ecole Supérieure de Biotechnologie Strasbourg, UMR 7242, CNRS, University of Strasbourg, Illkirch, France
Gallego, Carmen; INSERM UMR 996, Inflammation Microbiome and Immunosurveillance, University of Paris-Saclay, Clamart, France
Hendrick, Elodie ; Université de Liège - ULiège > GIGA > GIGA Cancer - Experimental Pathology
Pilard, Charlotte ; Université de Liège - ULiège > GIGA > GIGA Cancer - Experimental Pathology
Lerho, Thomas ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Reynders, Célia ; Université de Liège - ULiège > GIGA > GIGA Cancer - Experimental Pathology
Ancion, Marie ; Université de Liège - ULiège > GIGA > GIGA Cancer - Experimental Pathology
GREIMERS, Roland ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques
Twizere, Jean-Claude ; Université de Liège - ULiège > Département GxABT > Microbial, food and biobased technologies
Daube, Georges ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Schlecht-Louf, Geraldine ; INSERM UMR 996, Inflammation Microbiome and Immunosurveillance, University of Paris-Saclay, Clamart, France
Bachelerie, Françoise; INSERM UMR 996, Inflammation Microbiome and Immunosurveillance, University of Paris-Saclay, Clamart, France
Combes, Jean-Damien; Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France
MELIN, Pierrette ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Fillet, Marianne ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
DELVENNE, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'anatomie et cytologie pathologiques
Hubert, Pascale ; Université de Liège - ULiège > GIGA > GIGA Cancer - Experimental Pathology
Herfs, Michael ; Université de Liège - ULiège > GIGA > GIGA Cancer - Experimental Pathology
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding text :
We thank the Biobank of the University of Liege, the Laboratory of Clinical Microbiology as well as the GIGA-Immunohistochemistry, in vitro imaging, genomics and viral vectors facilities (University of Liege) for their assistance. We are also grateful to Dr Stephanie Gofflot, Dr Wouter Coppieters, Dr Emmanuel Di Valentin, Manon Deckers, Latifa Karim, Cecile Meex, Raphael Thonon, Kamilia El Kandoussi, and Nancy Rosiere for their technical assistance. We sincerely thank Prof Bernard Joris and Dr Ana Amoroso (Laboratory of Bacterial Physiology and Genetics, University of Liege), Prof Christine Jacobs-Wagner (Microbial Sciences Institute, Yale University) as well as Dr Olivier Peulen (Metastasis Research Laboratory, University of Liege) for helpful discussions. This work was supported in part by the University of Liege [Crédits Sectoriels de Recherche en Sciences de la Santé 2018-2020 (M.H.)], the Belgian Fund for Scientific Research [FNRS; MIS F.4520.20, CDR J.0088.21 (M.H.)], the Televie [PDR Televie 7.8507.19 (M.H.)], the Léon Frédéricq Foundation and the Seventh Framework Program for Research and Technological Development [European Commission: Infect-ERA 2015 (HPV-Motiva)]. C.P., T.L., C.R., and M.A. are Televie/FRIA fellows. A.L., D.B., and EloH are postdoctoral researchers. MH is a Research Associate at the FNRS.We thank the Biobank of the University of Liege, the Laboratory of Clinical Microbiology as well as the GIGA-Immunohistochemistry, in vitro imaging, genomics and viral vectors facilities (University of Liege) for their assistance. We are also grateful to Dr Stephanie Gofflot, Dr Wouter Coppieters, Dr Emmanuel Di Valentin, Manon Deckers, Latifa Karim, Cecile Meex, Raphael Thonon, Kamilia El Kandoussi, and Nancy Rosiere for their technical assistance. We sincerely thank Prof Bernard Joris and Dr Ana Amoroso (Laboratory of Bacterial Physiology and Genetics, University of Liege), Prof Christine Jacobs-Wagner (Microbial Sciences Institute, Yale University) as well as Dr Olivier Peulen (Metastasis Research Laboratory, University of Liege) for helpful discussions. This work was supported in part by the University of Liege [Cr?dits Sectoriels de Recherche en Sciences de la Sant? 2018-2020 (M.H.)], the Belgian Fund for Scientific Research [FNRS; MIS F.4520.20, CDR J.0088.21 (M.H.)], the Televie [PDR Televie 7.8507.19 (M.H.)], the L?on Fr?d?ricq Foundation and the Seventh Framework Program for Research and Technological Development [European Commission: Infect-ERA 2015 (HPV-Motiva)]. C.P., T.L., C.R., and M.A. are Televie/FRIA fellows. A.L., D.B., and EloH are postdoctoral researchers. MH is a Research Associate at the FNRS.
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