Tumour Virus Research最新文献

{"title":"Precise identification of viral–host integration events in HPV-positive cervical cancers by targeted long-read sequencing","authors":"Preetiparna Parida ,&nbsp;Nivedita Mukherjee ,&nbsp;Agastya Singh ,&nbsp;Shirley Lewis ,&nbsp;Krishna Sharan ,&nbsp;Sandeep Mallya ,&nbsp;Ashima Singh ,&nbsp;Surya Sarathi Das ,&nbsp;Mahadev Rao ,&nbsp;Daniel S. Higginson ,&nbsp;Radhakrishnan Sabarinathan ,&nbsp;Rama Rao Damerla","doi":"10.1016/j.tvr.2025.200325","DOIUrl":"10.1016/j.tvr.2025.200325","url":null,"abstract":"<div><div>Human papillomaviral (HPV) integrations into host human genome, a frequently observed event in HPV associated cervical cancer, are currently mapped through expensive Whole Genome sequencing (WGS) or RNA sequencing (RNA-seq) methodologies. This study aims to develop a targeted sequencing assay to determine HPV integrations in cervical tumors without the need for WGS or RNA-seq. We employed a library preparation strategy using tiled single primers that bind to HPV genome as a template and possibly extend HPV sequences into adjacent host human genomic sequences resulting in HPV and human chimeric sequences. Using this strategy, we sequenced known HPV integrations in HPV18 positive HeLa and HPV16 positive SiHa cell lines. We further used this method to detect HPV integration sites in four HPV-positive cervical cancer patients and confirmed these integration breakpoints by WGS and Sanger sequencing. Functional impact of HPV integrations was explored through differentially expressed genes within or near topologically associating domain (TAD) boundaries, possibly disrupted by respective integration events in these patients. We found <em>ZFP36L1, CPA3, CPB1</em> and <em>CXCL8</em> as some of the differentially expressed genes within disrupted TADs, which are known cancer associated genes. Our approach also reduced the cost of HPV integration detection by 90 % compared to WGS while also minimizing sequencing data volume. We believe that this method captures HPV integrations at significantly reduced costs and lesser sequencing data volume leading to better understanding of disease progression and monitoring cancer treatment.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200325"},"PeriodicalIF":4.7,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent integration of domestic cat hepatitis B virus DNA near feline CCNE1 supports an oncogenic role in hepatocellular carcinoma in cats.","authors":"João P Cavasin, Min-Chun Chen, Harout Ajoyan, Melanie J Dobromylskyj, Wei-Hsiang Huang, Mason Jager, Kate Van Brussel, Rebecca Rockett, Omid Nekouei, Penny Watson, Jason Bestwick, Yan Ru Choi, Jonathan A Lidbury, John M Cullen, Edward Holmes, Jörg M Steiner, Thomas Tu, Julia A Beatty","doi":"10.1016/j.tvr.2025.200324","DOIUrl":"https://doi.org/10.1016/j.tvr.2025.200324","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC) in humans. Domestic cat hepatitis B virus (DCHBV) naturally infects cats worldwide, but the oncogenic potential of this hepadnavirus is unclear. We investigated whether DCHBV contributes to feline HCC. Feline liver biopsies diagnosed with HCC (cases) and lymphocytic cholangitis (controls) were tested for DCHBV DNA by PCR. DCHBV-positive HCCs were further characterised by in situ hybridisation (ISH), whole-genome sequencing (WGS) and phylogenetic analysis. Targeted capture sequencing was used to identify and map viral DNA integrations. DCHBV DNA was detected in 17/71 (23.9%) HCCs versus 0/88 controls (P < 0.001). ISH confirmed hepatocyte-specific viral localization. Phylogenetic analysis placed six viruses in genotype A, and a seventh divergent virus in genotype B virus. Virus-host chimeric sequences, consistent with integration sites, were identified in 11/16 PCR-positive HCCs. Eight of the 11 integration sites were independently confirmed with WGS. Viral termini in integrated DCHBV sequences corresponded to double-stranded linear DNA, the substrate for HBV integration. Five unique DCHBV integrations fell within, or were adjacent to, the promoter of the feline homologue of proto-oncogene CCNE1, a recurrent target for HBV integration in human HCC. Our findings reveal a compelling association between DCHBV detection and HCC in cats. Critically, virus integration in DCHBV-associated HCC is described for the first time, supporting that, like HBV, DCHBV can promote hepatocarcinogenesis by insertional mutagenesis. Clarification of fundamental DCHBV virology in vitro, and the consequences of natural infection could advance disease-prevention strategies for feline and human patients.</p>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":" ","pages":"200324"},"PeriodicalIF":4.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The immunological heterogeneity of squamous cell carcinoma and adenocarcinoma of the uterine cervix: a systematic review","authors":"Marije Adriana Strikwerda ,&nbsp;Sabrina Anouck Weerstand ,&nbsp;George Louis Burchell ,&nbsp;Jacqueline Maria Tromp ,&nbsp;Constantijne Helene Mom ,&nbsp;Tanja Denise de Gruijl","doi":"10.1016/j.tvr.2025.200323","DOIUrl":"10.1016/j.tvr.2025.200323","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer is the fourth most common malignancy in women worldwide and generally driven by persistent infection with high-risk human papillomavirus. Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the two most common histological subtypes, with a relative increase in adenocarcinomas in the last decades. The immunological differences between cervical squamous cell carcinoma and adenocarcinoma remain largely unexplored. Understanding these distinctions is crucial for developing tailored therapies that can improve treatment outcomes for patients with cervical cancer. This systematic review provides an overview of the immunological features of squamous cell carcinoma and adenocarcinoma of the uterine cervix.</div></div><div><h3>Methods</h3><div>A systematic search was performed in PubMed, Embase.com, Web of Science, and Cochrane Library. All articles addressing immunological features of squamous cell carcinoma and adenocarcinoma of the uterine cervix were reviewed and included based on predefined inclusion and exclusion criteria.</div></div><div><h3>Results</h3><div>In total, 3207 articles were screened, of which 43 were included. Studies show that cervical squamous cell carcinomas are characterised by a more inflamed tumour microenvironment, but also contain more regulatory T cells and immune checkpoints. In contrast, adenocarcinomas are characterised by lower immune cell infiltration, contributing to its poorer prognosis and more limited response to treatment.</div></div><div><h3>Conclusion</h3><div>The observed differences emphasize the need for further research into subtype-specific differences and distinct therapeutic strategies. For squamous cell carcinomas, future research should focus on combinatorial immune checkpoint blockade, including regulatory T cell-depleting strategies. For adenocarcinomas, oncolytic virotherapy, therapeutic vaccination, and oncogenic signalling interference should be explored.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200323"},"PeriodicalIF":4.7,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144596442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human cytomegalovirus UL82 promotes colorectal cancer cell proliferation through inhibiting the ubiquitination of OGDH via ANGPT2","authors":"Lanni Wang ,&nbsp;Ruini Li ,&nbsp;Haitao Ren ,&nbsp;Chaoyi Jiang ,&nbsp;Ye Shi ,&nbsp;Bing Wang ,&nbsp;Wenyu Jin ,&nbsp;Jiaxue Wang ,&nbsp;Linhua Lan ,&nbsp;Feng Xu ,&nbsp;Guangxin Xiang ,&nbsp;Xiaoqun Zheng","doi":"10.1016/j.tvr.2025.200322","DOIUrl":"10.1016/j.tvr.2025.200322","url":null,"abstract":"<div><div>Human cytomegalovirus (HCMV) infection and its association with tumorigenesis and tumor progression have garnered increasing attention. Previous research results have indicated that the detection rate of HCMV <em>UL82</em> is higher in colorectal cancer (CRC) tissues and is correlated with poor prognosis in patients, yet the underlying mechanisms remain unclear. In this study, a cell model transfected with UL82 was established. Through <em>in vitro</em> and <em>in vivo</em> experiments, it was found that UL82 promoted the proliferation of CRC cells. Transcriptomic and metabolomic analyses revealed that UL82 could influence CRC glucose metabolism and cell proliferation by upregulating the key TCA cycle enzyme OGDH. Additionally, UL82 also affected CRC cell proliferation by upregulating the expression of ANGPT2, and silencing ANGPT2 resulted in a reduction in OGDH protein levels. Finally, through the investigation of the ubiquitin-mediated degradation pathway of OGDH, it was demonstrated that ANGPT2 inhibited the protein degradation of OGDH via deubiquitination, thereby maintaining its stability. In summary, UL82 promotes CRC cell proliferation by upregulating ANGPT2, which inhibits the ubiquitin-mediated degradation of OGDH, suggesting that targeting the UL82/ANGPT2/OGDH axis may offer a potential clinical strategy for the diagnosis of CRC.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200322"},"PeriodicalIF":4.7,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial board member","authors":"","doi":"10.1016/S2666-6790(25)00008-4","DOIUrl":"10.1016/S2666-6790(25)00008-4","url":null,"abstract":"","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200320"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical performance of the SureX PCR HPV test versus hybrid capture assays (DH2/careHPV) in primary cervical cancer screening","authors":"Yumei Ouyang ,&nbsp;Guzhanuer Abuduxikuer ,&nbsp;Tangnuer Abulimiti ,&nbsp;Guligeina Abudurexiti ,&nbsp;Qian Zhuo ,&nbsp;Wenyun Li ,&nbsp;Kadeliya Muhetaer ,&nbsp;Shaliya Abuduwufu ,&nbsp;Gulixian Tuerxun ,&nbsp;Remila Rezhake ,&nbsp;Guzhalinuer Abulizi","doi":"10.1016/j.tvr.2025.200319","DOIUrl":"10.1016/j.tvr.2025.200319","url":null,"abstract":"<div><h3>Background</h3><div>Evaluating novel human papillomavirus (HPV) tests in well-designed, population-based screening studies is essential for ensuring the benefits of cervical cancer screening.</div></div><div><h3>Methods</h3><div>8638 women aged over 25 years from China underwent HPV screening using a PCR-based full genotyping HPV assay (SureX HPV), alongside hybrid-capture HPV tests (DH2/careHPV) and cytology. Any abnormal results triggered colposcopy and biopsy if indicated. Screening performance was evaluated for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+.</div></div><div><h3>Results</h3><div>The high-risk HPV (hrHPV) positive rate by SureX HPV was significantly higher than by careHPV (11.0 % vs. 8.2 %, <em>P</em> &lt;0.01) but similar to DH2 HPV (12.0 % vs. 11.5 %, <em>P</em> =0.34). The overall agreement rates between SureX HPV and careHPV/DH2 HPV were 93.5 % (Kappa=0.63) and 94.0 % (Kappa=0.71). For CIN2+ detection, SureX HPV showed not-significantly higher sensitivity than careHPV (91.2 % vs 82.5 %, <em>P</em> =0.18) but lower specificity (91.2 % vs. 93.1 %, <em>P</em> &lt;0.01). Compared to DH2, SureX HPV demonstrated comparable sensitivity (95.7 % for both, <em>P</em> =1.0) and specificity (89.5 % vs. 90.2 %, <em>P</em> =0.21). Similar patterns were observed for CIN3+ detection. The area under the receiver operating characteristic curve (AUC) for the SureX HPV was similar to hybrid-capture HPV tests (<em>P</em> &gt;0.05 for both) and significantly higher than the cytology (ASC-US+) test for CIN2+/CIN3+ detection (<em>P</em> &lt;0.05 for both).</div></div><div><h3>Conclusions</h3><div>The PCR-based SureX HPV test demonstrated good concordance with well-validated hybrid-capture HPV tests in detecting hrHPV and CIN2+/CIN3+. Despite its slightly suboptimal specificity, SureX HPV could be an alternative in primary screening due to its full genotyping capability.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200319"},"PeriodicalIF":4.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the performance of the Xpert HPV assay in detecting HPV positive cases in Morocco","authors":"Said Ali Yerim ,&nbsp;Youssef Chami Khazraji ,&nbsp;Rachid Bekkali ,&nbsp;Maria Bennai ,&nbsp;Nassiba Bahra ,&nbsp;Imane Chaoui ,&nbsp;Fatima Zahra Chellat ,&nbsp;Zineb Gaizi ,&nbsp;Nabil Tachfouti ,&nbsp;Anas Benabdellah ,&nbsp;Bouchra Belkadi ,&nbsp;Mohammed Attaleb ,&nbsp;Mohamed Amine Berraho ,&nbsp;Mohammed El Mzibri","doi":"10.1016/j.tvr.2025.200318","DOIUrl":"10.1016/j.tvr.2025.200318","url":null,"abstract":"<div><div>Recently, the World Health Organization recommended integrating HPV testing into cervical cancer screening programs globally. This study aimed to compare the GeneXpert assay with PCR-sequencing for HPV detection and genotyping to assess the feasibility of incorporating HPV molecular testing into cervical cancer screening. A total of 1000 women aged 30 or 40 from rural and urban areas across four regions in Morocco with high sexually transmitted infection prevalence were recruited. After excluding 21 invalid tests, DNA testing on the remaining 979 samples showed an HPV prevalence of 4.0 % (39/979) by PCR and 5.0 % (49/979) by Xpert, with an overall prevalence of 5.7 % (56/979) when combining both techniques. The concordance rate between the tests was 97.5 %. Notably, the Xpert HPV assay was highly efficient in detecting HPV, with nearly all identified HPVs being high-risk oncogenic types, predominantly HPV16, 18, 31, 35, and 45.</div><div>The Xpert HPV assay has demonstrated excellent analytical performance, making it a reliable option for HPV detection in vaginal and cervical swabs. Its integration into primary cervical cancer screening programs could significantly enhance the early detection of HPV-positive cases, thereby strengthening the screening framework and potentially reducing both the incidence and mortality of cervical cancer. Future studies should focus on confirming these results and exploring the utility of this method in conjunction with other diagnostic tools such as visual inspection with acetic acid (VIA) for a comprehensive assessment of its effectiveness in real-world settings.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200318"},"PeriodicalIF":4.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daxx and HIRA go viral – How chromatin remodeling complexes affect DNA virus infection","authors":"Julia Mai ,&nbsp;Masih Nazari ,&nbsp;Thomas Stamminger ,&nbsp;Sabrina Schreiner","doi":"10.1016/j.tvr.2025.200317","DOIUrl":"10.1016/j.tvr.2025.200317","url":null,"abstract":"<div><div>Daxx and HIRA are key proteins in the host response to DNA virus infections. Daxx is involved in apoptosis, transcription regulation, and stress responses. During DNA virus infections, Daxx helps modulate the immune response and viral progression. Viruses like adenoviruses and herpesviruses can exploit Daxx to evade immune detection, either by targeting it for degradation or inhibiting its function. Daxx also interacts with chromatin to regulate transcription, which viruses can manipulate to enhance their own gene expression and replication. HIRA is a histone chaperone and reported to be essential for chromatin assembly and gene regulation. It plays a critical role in maintaining chromatin structure and modulating gene accessibility. During DNA virus infection, HIRA influences chromatin remodeling, affecting both viral and host DNA accessibility, which impacts viral replication and gene expression. Additionally, the histone variant H3.3 is crucial for maintaining active chromatin states. It is incorporated into chromatin independently of DNA replication and is associated with active gene regions. During viral infections, H3.3 dynamics can be altered, affecting viral genome accessibility and replication efficiency. Overall, Daxx and HIRA are integral to orchestrating viral infection programs, maintaining latency and/or persistence, and influencing virus-induced transformation by modulating chromatin dynamics and host immune responses, making them significant targets for therapeutic strategies once fully understood. Here, we summarize various DNA viruses and their crosstalk with Daxx and HIRA.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200317"},"PeriodicalIF":4.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drosophila model of HPV18-Induced pathogenesis reveals a role for E6 oncogene in regulation of NF-κB and Wnt to inhibit apoptosis","authors":"Mojgan Padash Barmchi ,&nbsp;Rami N. Hassan ,&nbsp;Mehrnaz Afkhami ,&nbsp;John P. Masly ,&nbsp;Harrison Brown ,&nbsp;Quincy P. Collins ,&nbsp;Michael J. Grunsted","doi":"10.1016/j.tvr.2025.200316","DOIUrl":"10.1016/j.tvr.2025.200316","url":null,"abstract":"<div><div>Cancers caused by high-risk human papillomavirus (HPV) remain a significant health threat resulting in more than 300,000 deaths, annually. Persistent expression of two HPV oncogenes, E6 and E7, are necessary for cancer development and progression. E6 has several functions contributing to tumorigenesis one of which is blocking programmed cell death, apoptosis. The detailed mechanism of anti-apoptosis function of E6 is not fully understood. Here, using a <em>Drosophila</em> model of HPV18E6 and the human UBE3A-induced pathogenesis, we show that anti-apoptotic function of E6 is conserved in <em>Drosophila</em>. We demonstrate that the <em>Drosophila</em> homologs of human NF-κB transcription factors, Dorsal and Dif are proapoptotic. They induce the expression of Wingless (Wg, the <em>Drosophila</em> homolog of human Wnt), leading to apoptosis. Our results indicate that E6 oncogene inhibits apoptosis by downregulating the expression of Wg, Dorsal, and Dif. Additionally, we find that Dorsal and Dif, not only promote apoptosis but also regulate autophagy and necrosis. Dorsal promotes autophagy while Dif counteracts it, inducing the formation of acidic vacuoles and necrosis. Interestingly, although E6 blocks the proapoptotic function of Dorsal and Dif, it lacks the ability to interfere with their role in apoptosis-independent cell death. Given the high conservation of NF-κB transcription factors our results provide new insight into potential mechanisms mediated by NF-κB to intervene with cell immortalization action of E6 oncoprotein in HPV-infected cells.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200316"},"PeriodicalIF":4.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of epithelial growth factor receptors by the oncoprotein E5 during the HPV16 differentiation-dependent life cycle","authors":"Mariano A. Molina ,&nbsp;Sneha Biswas ,&nbsp;Omar Jiménez-Vázquez ,&nbsp;Jason M. Bodily","doi":"10.1016/j.tvr.2025.200315","DOIUrl":"10.1016/j.tvr.2025.200315","url":null,"abstract":"<div><div>Human papillomavirus (HPV) 16 infection initiates upon viral entry into the basal cells of the epithelium. The virus manipulates signaling pathways to complete its life cycle, which depends on cellular differentiation. The virus expresses the oncoproteins E5, E6, and E7 to promote immune evasion, cell cycle progression, apoptosis inhibition, and viral replication. The least studied viral oncoprotein is E5 (16E5), which can regulate epithelial growth factor receptor (GFR) signaling pathways. GFRs such as transforming growth factor-beta receptor (TGFBR), epidermal growth factor receptor (EGFR), and keratinocyte growth factor receptor (KGFR) have essential roles in cell growth, differentiation, and proliferation. These receptors obtain their ligands from the microenvironment, and once activated, regulate cellular behavior in the epithelium. GFRs therefore represent valuable targets for the virus to establish and maintain a cellular environment supportive of infection. The ability of 16E5 to regulate proliferation and differentiation varies through the differentiating epithelium, making it necessary to adequately describe the association between 16E5 and GFRs. Here we summarize the regulation of GFR signaling pathways by 16E5, discuss the roles of stromal growth factors, and outline unresolved questions over cellular differentiation and proliferation during the HPV life cycle.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200315"},"PeriodicalIF":4.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}