Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes
Persistent human papillomavirus (HPV) infection is necessary but insufficient for viral oncogenesis. Additional contributing co-factors, such as immune evasion and viral integration have been implicated in HPV-induced cancer progression. It is widely accepted that HPV + keratinocytes require co-cult...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Tumour Virus Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666679024000260 |
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| author | Claire D. James Rachel L. Lewis Austin J. Witt Christiane Carter Nabiha M. Rais Xu Wang Molly L. Bristol |
| author_facet | Claire D. James Rachel L. Lewis Austin J. Witt Christiane Carter Nabiha M. Rais Xu Wang Molly L. Bristol |
| author_sort | Claire D. James |
| collection | DOAJ |
| description | Persistent human papillomavirus (HPV) infection is necessary but insufficient for viral oncogenesis. Additional contributing co-factors, such as immune evasion and viral integration have been implicated in HPV-induced cancer progression. It is widely accepted that HPV + keratinocytes require co-culture with fibroblasts to maintain viral DNA as episomes. How fibroblasts regulate viral episome maintenance is a critical knowledge gap. Here we present comprehensive RNA sequencing and proteomic analysis demonstrating that coculture with fibroblasts is supportive of the viral life cycle, and is confirmatory of previous observations. Novel observations suggest that errors in “cross-talk” between fibroblasts and infected keratinocytes may regulate HPV integration and drive oncogenic progression. Our co-culture models offer new insights into HPV-related transformation mechanisms. |
| format | Article |
| id | doaj-art-d1605d99e6be4359af2373cacdd4f56e |
| institution | OA Journals |
| issn | 2666-6790 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Tumour Virus Research |
| spelling | doaj-art-d1605d99e6be4359af2373cacdd4f56e2025-08-20T02:06:19ZengElsevierTumour Virus Research2666-67902025-06-011920030210.1016/j.tvr.2024.200302Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytesClaire D. James0Rachel L. Lewis1Austin J. Witt2Christiane Carter3Nabiha M. Rais4Xu Wang5Molly L. Bristol6Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA, USAPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA, USAPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA, USAVCU Massey Bioinformatics Shared Resource, Richmond, VA, USAPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA, USAPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA, USAPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA, USA; VCU Massey Comprehensive Cancer Center, Richmond, VA, USA; Corresponding author. Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA, USA.Persistent human papillomavirus (HPV) infection is necessary but insufficient for viral oncogenesis. Additional contributing co-factors, such as immune evasion and viral integration have been implicated in HPV-induced cancer progression. It is widely accepted that HPV + keratinocytes require co-culture with fibroblasts to maintain viral DNA as episomes. How fibroblasts regulate viral episome maintenance is a critical knowledge gap. Here we present comprehensive RNA sequencing and proteomic analysis demonstrating that coculture with fibroblasts is supportive of the viral life cycle, and is confirmatory of previous observations. Novel observations suggest that errors in “cross-talk” between fibroblasts and infected keratinocytes may regulate HPV integration and drive oncogenic progression. Our co-culture models offer new insights into HPV-related transformation mechanisms.http://www.sciencedirect.com/science/article/pii/S2666679024000260StromaHuman papillomavirusOropharyngeal cancerMicroenvironmentFibroblastsTranscriptional reprogramming |
| spellingShingle | Claire D. James Rachel L. Lewis Austin J. Witt Christiane Carter Nabiha M. Rais Xu Wang Molly L. Bristol Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes Tumour Virus Research Stroma Human papillomavirus Oropharyngeal cancer Microenvironment Fibroblasts Transcriptional reprogramming |
| title | Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes |
| title_full | Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes |
| title_fullStr | Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes |
| title_full_unstemmed | Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes |
| title_short | Fibroblasts regulate the transcriptional signature of human papillomavirus-positive keratinocytes |
| title_sort | fibroblasts regulate the transcriptional signature of human papillomavirus positive keratinocytes |
| topic | Stroma Human papillomavirus Oropharyngeal cancer Microenvironment Fibroblasts Transcriptional reprogramming |
| url | http://www.sciencedirect.com/science/article/pii/S2666679024000260 |
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