{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:24:45Z","timestamp":1787117085997,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cutaneous warts are common HPV-induced lesions with limited treatments for recalcitrant cases. Fatty-acid metabolism (FAM) maintains epidermal homeostasis, but whether papillomavirus infection actively suppresses FAM programs and whether restoring FAM-related regulators can modulate keratinocyte dysfunction remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We established a murine MmuPV1 wart model and performed bulk RNA-seq. FAM-related DEGs were identified via network analysis and machine learning. Immune infiltration was assessed by CIBERSORT.\n                      <jats:italic>In vitro<\/jats:italic>\n                      validation used HPV16 E6\/E7-transfected HaCaT cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Transcriptome analysis revealed significant suppression of FAM pathways in wart lesions. Four key FAM-related differentially expressed genes (Nr1h3, Dgat1, Scd1, and Fabp4) were identified from RNA-seq-based bioinformatic analyses and further supported by\n                      <jats:italic>in vitro<\/jats:italic>\n                      E6\/E7-related expression assays.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , HPV16 E6\/E7 expression reduced these genes in HaCaT keratinocytes. NR1H3 overexpression partially attenuated E6\/E7-induced proliferation and differentiation abnormalities, lipid-droplet accumulation, and IL-6\/CCL2 secretion, with partial restoration of ABCA1 expression and inhibition of NF-kB activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Papillomavirus infection is associated with coordinated suppression of FAM-related programs. NR1H3, Dgat1, Scd1, and Fabp4 represent candidate metabolic regulatory nodes; their therapeutic relevance requires further\n                      <jats:italic>in vivo<\/jats:italic>\n                      validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1860417","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:35:30Z","timestamp":1787114130000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cutaneous papillomaviruses infection rewires fatty-acid metabolism"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaoyan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Dermatology, Xiang\u2019an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"National Center of Technology Innovation for animal model. State Key Laboratory of Respiratory Health and Multimorbidity. Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education. NHC Key Laboratory of Comparative Medicine. Institute of Laboratory Animal Science, CAMS & PUMC","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzhou","family":"Cai","sequence":"additional","affiliation":[{"name":"National Center of Technology Innovation for animal model. State Key Laboratory of Respiratory Health and Multimorbidity. Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education. NHC Key Laboratory of Comparative Medicine. Institute of Laboratory Animal Science, CAMS & PUMC","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"National Center of Technology Innovation for animal model. State Key Laboratory of Respiratory Health and Multimorbidity. Key Laboratory of Pathogen Infection Prevention and Control (Peking Union Medical College), Ministry of Education. NHC Key Laboratory of Comparative Medicine. Institute of Laboratory Animal Science, CAMS & PUMC","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Liao","sequence":"additional","affiliation":[{"name":"Universite Paris Dauphine","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijun","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Xiang\u2019an Hospital of Xiamen University, School of Medicine, Xiamen University","place":["Xiamen, Fujian, China"]},{"name":"College of Mathematical Medicine, Zhejiang Normal University","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/lary.28026","article-title":"Infectivity of murine papillomavirus in the surgical byproducts of treated tail warts","volume":"130","author":"Best","year":"2020","journal-title":"Laryngoscope"},{"key":"B2","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.plefa.2010.02.005","article-title":"Lipid droplets in inflammation and cancer","volume":"82","author":"Bozza","year":"2010","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"B3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1172\/jci13880","article-title":"Leptin modulates the effects of acyl CoA:diacylglycerol acyltransferase deficiency on murine fur and sebaceous glands","volume":"109","author":"Chen","year":"2002","journal-title":"J. Clin. Invest."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e473","DOI":"10.1002\/onco.13593","article-title":"The impact of human papillomavirus infection on skin cancer: a population-based cohort study","volume":"26","author":"Chen","year":"2021","journal-title":"Oncologist"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/rmv.1822","article-title":"Human papillomavirus molecular biology and disease association","author":"Doorbar","year":"2015","journal-title":"Rev. Med. Virol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1007\/s00403-025-04022-3","article-title":"Efficacy of intralesional acyclovir versus quadrivalent human papillomavirus vaccine for treatment of recalcitrant cutaneous warts: a clinical trial","volume":"317","author":"Elyamany","year":"2025","journal-title":"Arch. Dermatol. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"38378","DOI":"10.1074\/jbc.M105805200","article-title":"27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells","volume":"276","author":"Fu","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306253","article-title":"A frog skin-derived peptide targeting SCD1 exerts radioprotective effects against skin injury by inhibiting STING-mediated inflammation","volume":"11","author":"Geng","year":"2024","journal-title":"Adv. Sci. (Weinh)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/v9090246","article-title":"The mouse papillomavirus infection model","volume":"9","author":"Hu","year":"2017","journal-title":"Viruses"},{"key":"B10","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nm820","article-title":"Reciprocal regulation of inflammation and lipid metabolism by liver X receptors","volume":"9","author":"Joseph","year":"2003","journal-title":"Nat. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: biological systems database as a model of the real world","volume":"53","author":"Kanehisa","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2020.552028","article-title":"Epidemiology and burden of human papillomavirus and related diseases, molecular pathogenesis, and vaccine evaluation","volume":"8","author":"Kombe Kombe","year":"2020","journal-title":"Front. Public Health"},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1080\/09546634.2020.1737635","article-title":"A comprehensive review of treatment options for recalcitrant nongenital cutaneous warts","volume":"33","author":"Leerunyakul","year":"2022","journal-title":"J. Dermatolog Treat."},{"key":"B14","first-page":"204","article-title":"Development of a mouse model of papillomavirus-mediated skin wart","volume":"29","author":"Li","year":"2021","journal-title":"Acta Laboratorium Animalis Scientia Sin."},{"key":"B15","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.bbalip.2013.09.016","article-title":"Fatty acid transporters in skin development, function and disease","volume":"1841","author":"Lin","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-194","article-title":"Modulation of cardiometabolic pathways in skin and serum from patients with psoriasis","volume":"11","author":"Mehta","year":"2013","journal-title":"J. Transl. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"195","DOI":"10.36849\/jdd.6424","article-title":"Intralesional bleomycin combined with cryotherapy in the treatment of recalcitrant verruca vulgaris","volume":"21","author":"Mesgarzadeh","year":"2022","journal-title":"J. Drugs Dermatol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and functions of lipid droplets","volume":"20","author":"Olzmann","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nature21379","article-title":"Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism","volume":"543","author":"Pan","year":"2017","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/s41586-021-04137-3","article-title":"A hormone complex of FABP4 and nucleoside kinases regulates islet function","volume":"600","author":"Prentice","year":"2021","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1111\/exd.14676","article-title":"Saprophytic bacteria and fungi colonize stearoyl coenzyme-A desaturase-1 knockout skin","volume":"32","author":"Pyle","year":"2023","journal-title":"Exp. Dermatol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2482","DOI":"10.1074\/jbc.R113.516716","article-title":"Role of stearoyl-CoA desaturase-1 in skin integrity and whole body energy balance","volume":"289","author":"Sampath","year":"2014","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1080\/09546634.2020.1732285","article-title":"Association of TLR2 and TLR4 gene polymorphism with susceptibility to wart infections and their response to candida antigen immunotherapy","volume":"33","author":"Tantawy","year":"2022","journal-title":"J. Dermatolog Treat."},{"key":"B24","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1053\/j.gastro.2018.03.040","article-title":"Intestinal failure and aberrant lipid metabolism in patients with DGAT1 deficiency","volume":"155","author":"van Rijn","year":"2018","journal-title":"Gastroenterology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"12097","DOI":"10.1073\/pnas.200367697","article-title":"Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha","volume":"97","author":"Venkateswaran","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B26","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.jdermsci.2020.01.009","article-title":"Ionizing radiation induces cutaneous lipid remolding and skin adipocytes confer protection against radiation-induced skin injury","volume":"97","author":"Xiao","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.1111\/jocd.13616","article-title":"A review of fatty acids influencing skin condition","volume":"19","author":"Yang","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/jebm.12494","article-title":"Clinical guideline for the diagnosis and treatment of cutaneous warts (2022)","volume":"15","author":"Zhu","year":"2022","journal-title":"J. Evid Based Med."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1860417\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:35:33Z","timestamp":1787114133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1860417\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":28,"alternative-id":["10.3389\/fcimb.2026.1860417"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1860417","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"article-number":"1860417"}}