HPV infection alters vaginal microbiome through down-regulating host mucosal innate peptides used by Lactobacilli as amino acid sources

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 and Michael Herfs ()
Additional contact information
Alizee Lebeau: University of Liege
Diane Bruyere: University of Liege
Patrick Roncarati: University of Liege
Paul Peixoto: University of Bourgogne Franche-Comté
Eric Hervouet: University of Bourgogne Franche-Comté
Gael Cobraiville: University of Liege
Bernard Taminiau: University of Liege
Murielle Masson: University of Strasbourg
Carmen Gallego: University of Paris-Saclay
Gabriel Mazzucchelli: University of Liege
Nicolas Smargiasso: University of Liege
Maximilien Fleron: University of Liege
Dominique Baiwir: University of Liege
Elodie Hendrick: University of Liege
Charlotte Pilard: University of Liege
Thomas Lerho: University of Liege
Celia Reynders: University of Liege
Marie Ancion: University of Liege
Roland Greimers: University Hospital Center of Liege
Jean-Claude Twizere: University of Liege
Georges Daube: University of Liege
Geraldine Schlecht-Louf: University of Paris-Saclay
Françoise Bachelerie: University of Paris-Saclay
Jean-Damien Combes: International Agency for Research on Cancer, World Health Organization
Pierrette Melin: University Hospital Center of Liege
Marianne Fillet: University of Liege
Philippe Delvenne: University of Liege
Pascale Hubert: University of Liege
Michael Herfs: University of Liege

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28724-8

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DOI: 10.1038/s41467-022-28724-8

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