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Stress keratin 17 enhances papillomavirus infection-induced disease by downregulating T cell recruitment.
PLoS Pathog 2020; 16(1):e1008206PP

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.

Authors+Show Affiliations

McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States of America.Department of Dermatology, University of Pennsylvania, Philadelphia, PA, United States of America.McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States of America.McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States of America.Tumor Virus RNA Biology Section, National Cancer Institute, Frederick, MD, United States of America.CCR Collaborative Bioinformatics Resource (CCBR), National Cancer Institute, Bethesda, MD, United States of America.McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States of America.McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States of America.Tumor Virus RNA Biology Section, National Cancer Institute, Frederick, MD, United States of America.McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31968015

Citation

Wang, Wei, et al. "Stress Keratin 17 Enhances Papillomavirus Infection-induced Disease By Downregulating T Cell Recruitment." PLoS Pathogens, vol. 16, no. 1, 2020, pp. e1008206.
Wang W, Uberoi A, Spurgeon M, et al. Stress keratin 17 enhances papillomavirus infection-induced disease by downregulating T cell recruitment. PLoS Pathog. 2020;16(1):e1008206.
Wang, W., Uberoi, A., Spurgeon, M., Gronski, E., Majerciak, V., Lobanov, A., ... Lambert, P. F. (2020). Stress keratin 17 enhances papillomavirus infection-induced disease by downregulating T cell recruitment. PLoS Pathogens, 16(1), pp. e1008206. doi:10.1371/journal.ppat.1008206.
Wang W, et al. Stress Keratin 17 Enhances Papillomavirus Infection-induced Disease By Downregulating T Cell Recruitment. PLoS Pathog. 2020;16(1):e1008206. PubMed PMID: 31968015.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stress keratin 17 enhances papillomavirus infection-induced disease by downregulating T cell recruitment. AU - Wang,Wei, AU - Uberoi,Aayushi, AU - Spurgeon,Megan, AU - Gronski,Ellery, AU - Majerciak,Vladimir, AU - Lobanov,Alexei, AU - Hayes,Mitchell, AU - Loke,Amanda, AU - Zheng,Zhi-Ming, AU - Lambert,Paul F, Y1 - 2020/01/22/ PY - 2019/09/12/received PY - 2019/11/12/accepted PY - 2020/1/23/entrez PY - 2020/1/23/pubmed PY - 2020/1/23/medline SP - e1008206 EP - e1008206 JF - PLoS pathogens JO - PLoS Pathog. VL - 16 IS - 1 N2 - 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. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/31968015/Stress_keratin_17_enhances_papillomavirus_infection-induced_disease_by_downregulating_T_cell_recruitment L2 - http://dx.plos.org/10.1371/journal.ppat.1008206 DB - PRIME DP - Unbound Medicine ER -