HPV infection alters vaginal microbiome through down-regulating host mucosal innate peptides used by Lactobacilli as amino acid sources
Year: 2022
Type: article
Abstract: 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.
Source: Nature Communications
Authors: Alizee Lebeau, Diane Bruyere, Patrick Roncarati, Paul Peixoto, Eric Hervouet, Gael Cobraiville, Bernard Taminiau, Murielle Masson, Carmen Gallego, Gabriel Mazzucchelli, Nicolas Smargiasso, Maximilien Fleron, Dominique Baiwir, Elodie Hendrick, Charlotte Pilard, Thomas Lerho, Celia Reynders, Marie Ancion, Roland Greimers, Jean-Claude Twizere, Georges Daube, Geraldine Schlecht-Louf, Françoise Bachelerie, Jean-Damien Combes, Pierrette Melin, Marianne Fillet, Philippe Delvenne, Pascale Hubert, Michael Herfs
Institutions: University of Liège, Inserm, Université Bourgogne Franche-Comté, Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, Centre National de la Recherche Scientifique, École Supérieure de Biotechnologie de Strasbourg, Biotechnologie et Signalisation Cellulaire, Université de Strasbourg, Université Paris-Saclay, Inflammation, Microbiome and Immunosurveillance, Centre Hospitalier Universitaire de Liège, World Health Organization, Centre international de recherche sur le cancer
Language: English
Subfield: Microbiology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
OpenAlex ID: W4214740675