Stress Keratin 17 Enhances Papillomavirus Infection-induced Disease by Downregulating T Cell Recruitment

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2020 Jan 23

PMID 31968015

Citations 24

Authors

Wei Wang

Aayushi Uberoi

Megan Spurgeon

Ellery Gronski

Vladimir Majerciak

Alexei Lobanov

Mitchell Hayes

Amanda Loke

Zhi-Ming Zheng

Paul F Lambert

Affiliations

Soon will be listed here.

Abstract

High-risk human papillomaviruses (HPVs) cause 5% of human cancers. Despite the availability of HPV vaccines, there remains a strong urgency to find ways to treat persistent HPV infections, as current HPV vaccines are not therapeutic for individuals already infected. We used a mouse papillomavirus infection model to characterize virus-host interactions. We found that mouse papillomavirus (MmuPV1) suppresses host immune responses via overexpression of stress keratins. In mice deficient for stress keratin K17 (K17KO), we observed rapid regression of papillomas dependent on T cells. Cellular genes involved in immune response were differentially expressed in the papillomas arising on the K17KO mice correlating with increased numbers of infiltrating CD8+ T cells and upregulation of IFNγ-related genes, including CXCL9 and CXCL10, prior to complete regression. Blocking the receptor for CXCL9/CXCL10 prevented early regression. Our data provide a novel mechanism by which papillomavirus-infected cells evade host immunity and defines new therapeutic targets for treating persistent papillomavirus infections.

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