Pub Date : 2025-12-01Epub Date: 2025-11-01DOI: 10.1016/j.tvr.2025.200329
Ashley N. Della Fera, Dan Chen, Alison A. McBride
The circular, double-stranded DNA genomes of Human papillomaviruses (HPV) exist in a nucleosomal state throughout the infectious cycle and rely on host histone epigenetic modifications and chromatin assembly processes to promote various phases of the viral life cycle. Here, we show that the histone H3.3 chaperone HIRA and its associated complex members are recruited to HPV replication factories during the late phase of the HPV life cycle. HIRA is also recruited to HPV replication factories generated by amplification of a replicon with a minimal origin and expression of the viral replication proteins E1 and E2, demonstrating that the E1 and E2 proteins are sufficient for HIRA recruitment. Downregulation of HIRA expression reduces HPV31 DNA amplification and viral transcription in differentiated keratinocytes. Histone H3.3 that is highly phosphorylated on serine residue 31 is also enriched at sites of HPV replication and this modification links the DNA damage response to chromatin that supports rapid gene activation. We propose that deposition of histone H3.3 generates viral minichromosomes which are highly primed to support the late stages of the HPV life cycle.
{"title":"Chromatin assembly by the histone chaperone HIRA facilitates Human Papillomavirus replication","authors":"Ashley N. Della Fera, Dan Chen, Alison A. McBride","doi":"10.1016/j.tvr.2025.200329","DOIUrl":"10.1016/j.tvr.2025.200329","url":null,"abstract":"<div><div>The circular, double-stranded DNA genomes of Human papillomaviruses (HPV) exist in a nucleosomal state throughout the infectious cycle and rely on host histone epigenetic modifications and chromatin assembly processes to promote various phases of the viral life cycle. Here, we show that the histone H3.3 chaperone HIRA and its associated complex members are recruited to HPV replication factories during the late phase of the HPV life cycle. HIRA is also recruited to HPV replication factories generated by amplification of a replicon with a minimal origin and expression of the viral replication proteins E1 and E2, demonstrating that the E1 and E2 proteins are sufficient for HIRA recruitment. Downregulation of HIRA expression reduces HPV31 DNA amplification and viral transcription in differentiated keratinocytes. Histone H3.3 that is highly phosphorylated on serine residue 31 is also enriched at sites of HPV replication and this modification links the <span>DNA</span> damage response to chromatin that supports rapid gene activation. We propose that deposition of histone H3.3 generates viral minichromosomes which are highly primed to support the late stages of the HPV life cycle.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200329"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145439955","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}
Pub Date : 2025-12-01Epub Date: 2025-07-31DOI: 10.1016/j.tvr.2025.200326
Barry Milavetz, Ranna Dawlaty, Jacob Haugen
Since early and late transcription are both regulated from the same central regulatory region in SV40 chromatin, the location of nucleosomes carrying histone modifications may contribute to controlling the direction of transcription from the regulatory region. This could occur through the generation of active chromatin in the direction of transcription and repressive chromatin in the opposite direction. In order to test this hypothesis, we have characterized the products of SV40 transcription and location of nucleosomes carrying histone modifications in SV40 chromatin following treatment of infected cells with inhibitors of histone methylation metabolism. The inhibitors used included GSK-LSD1 to inhibit demethylation of H3K4me1 and H3K9me1, A366 to inhibit the introduction of H3K9me1, and UNC1999 to inhibit the introduction of H3K27me3. The results are consistent with a regulatory model in which nucleosomes carrying H3K9me1 and H3K27me3 located at the ends of the SV40 regulatory region act to regulate transcription.
{"title":"Dysregulation of histone methylation in SV40 chromosomes during replication results in aberrant transcription and chromatin structure.","authors":"Barry Milavetz, Ranna Dawlaty, Jacob Haugen","doi":"10.1016/j.tvr.2025.200326","DOIUrl":"10.1016/j.tvr.2025.200326","url":null,"abstract":"<p><p>Since early and late transcription are both regulated from the same central regulatory region in SV40 chromatin, the location of nucleosomes carrying histone modifications may contribute to controlling the direction of transcription from the regulatory region. This could occur through the generation of active chromatin in the direction of transcription and repressive chromatin in the opposite direction. In order to test this hypothesis, we have characterized the products of SV40 transcription and location of nucleosomes carrying histone modifications in SV40 chromatin following treatment of infected cells with inhibitors of histone methylation metabolism. The inhibitors used included GSK-LSD1 to inhibit demethylation of H3K4me1 and H3K9me1, A366 to inhibit the introduction of H3K9me1, and UNC1999 to inhibit the introduction of H3K27me3. The results are consistent with a regulatory model in which nucleosomes carrying H3K9me1 and H3K27me3 located at the ends of the SV40 regulatory region act to regulate transcription.</p>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":" ","pages":"200326"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769303","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}
Pub Date : 2025-12-01Epub Date: 2025-11-26DOI: 10.1016/j.tvr.2025.200333
GuoXiu Cao , Chan Ding , Jun Dai , Xusheng Qiu
As a promising cancer treatment strategy, oncolytic viruses (OVs) selectively replicate and kill tumor cells while sparing normal cells. They improve the tumor immunosuppressive microenvironment through multiple mechanisms, including direct infection, replication, and lysis of tumor cells—leading to the release of tumor-associated antigens (TAAs), chemokines, and cytokines, which in turn induce immunogenic cell death (ICD) and trigger sustained antitumor immune responses. Currently, while OVs have demonstrated therapeutic efficacy in multiple preclinical and clinical studies, their monotherapy fails to benefit a broad spectrum of cancer patients. Therefore, there remains a need to fully understand the biological mechanisms of OVs and optimize immunotherapeutic strategies to benefit more cancer patients and enhance therapeutic efficacy. In this review, we discuss how the immune responses induced by OVs maintain a balance between antiviral and antitumor immunity, as well as their unique characteristics in inducing ICD. In addition, we describe how to enhance the efficacy of cancer immunotherapy by combining OVs therapy with ICD inducers, aiming to provide valuable insights to guide the development of clinical OVs -based therapies.
{"title":"Oncolytic virus and immunogenic cell death in cancer therapy","authors":"GuoXiu Cao , Chan Ding , Jun Dai , Xusheng Qiu","doi":"10.1016/j.tvr.2025.200333","DOIUrl":"10.1016/j.tvr.2025.200333","url":null,"abstract":"<div><div>As a promising cancer treatment strategy, oncolytic viruses (OVs) selectively replicate and kill tumor cells while sparing normal cells. They improve the tumor immunosuppressive microenvironment through multiple mechanisms, including direct infection, replication, and lysis of tumor cells—leading to the release of tumor-associated antigens (TAAs), chemokines, and cytokines, which in turn induce immunogenic cell death (ICD) and trigger sustained antitumor immune responses. Currently, while OVs have demonstrated therapeutic efficacy in multiple preclinical and clinical studies, their monotherapy fails to benefit a broad spectrum of cancer patients. Therefore, there remains a need to fully understand the biological mechanisms of OVs and optimize immunotherapeutic strategies to benefit more cancer patients and enhance therapeutic efficacy. In this review, we discuss how the immune responses induced by OVs maintain a balance between antiviral and antitumor immunity, as well as their unique characteristics in inducing ICD. In addition, we describe how to enhance the efficacy of cancer immunotherapy by combining OVs therapy with ICD inducers, aiming to provide valuable insights to guide the development of clinical OVs -based therapies.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"20 ","pages":"Article 200333"},"PeriodicalIF":8.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145641871","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}
Pub Date : 2025-12-01Epub Date: 2025-07-17DOI: 10.1016/j.tvr.2025.200325
Preetiparna Parida , Nivedita Mukherjee , Agastya Singh , Shirley Lewis , Krishna Sharan , Sandeep Mallya , Ashima Singh , Surya Sarathi Das , Mahadev Rao , Daniel S. Higginson , Radhakrishnan Sabarinathan , Rama Rao Damerla
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 ZFP36L1, CPA3, CPB1 and CXCL8 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.
{"title":"Precise identification of viral–host integration events in HPV-positive cervical cancers by targeted long-read sequencing","authors":"Preetiparna Parida , Nivedita Mukherjee , Agastya Singh , Shirley Lewis , Krishna Sharan , Sandeep Mallya , Ashima Singh , Surya Sarathi Das , Mahadev Rao , Daniel S. Higginson , Radhakrishnan Sabarinathan , 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":"2025-12-01","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}
Pub Date : 2025-06-01Epub Date: 2025-02-07DOI: 10.1016/j.tvr.2025.200314
Kemi Hannah Oladipo , Joanna L. Parish
Human papillomaviruses (HPVs) cause diseases ranging from benign warts to invasive cancers. HPVs are the cause of almost all cervical cancers and a sub-set of other epithelial malignancies including head and neck cancers, specifically within the oropharynx. The oncogenic properties of HPV are largely mediated through the viral oncoproteins E6 and E7, which disrupt many cellular pathways to drive uncontrolled cell proliferation. One family of proteins targeted by HPV is the Aurora kinase family. Aurora kinases are serine/threonine kinases including Aurora kinase A (AURKA), B (AURKB), and C (AURKC) which are often dysregulated in many cancer types, including HPV driven cancers. All three family members play essential roles in mitotic regulation and accurate cell division.
The deregulation of Aurora kinases by HPV infection highlights their potential as therapeutic targets in HPV-associated malignancies. Targeting Aurora kinase activity, in combination with current HPV therapies, may provide new avenues for treating HPV-induced cancers and reducing the burden of HPV-related diseases. Combinatorial inhibition targets distinct but overlapping functions of these kinases, thereby reducing the potential for cancer cells to develop resistance. This broad impact emphasizes the capability for Aurora kinase inhibitors not only as anti-mitotic agents but also as modulators of multiple oncogenic pathways. This review explores the combinatorial effects of Aurora kinase inhibition, offering insights into novel therapeutic strategies for the treatment of HPV-driven cancers.
{"title":"De-regulation of aurora kinases by oncogenic HPV; implications in cancer development and treatment","authors":"Kemi Hannah Oladipo , Joanna L. Parish","doi":"10.1016/j.tvr.2025.200314","DOIUrl":"10.1016/j.tvr.2025.200314","url":null,"abstract":"<div><div>Human papillomaviruses (HPVs) cause diseases ranging from benign warts to invasive cancers. HPVs are the cause of almost all cervical cancers and a sub-set of other epithelial malignancies including head and neck cancers, specifically within the oropharynx. The oncogenic properties of HPV are largely mediated through the viral oncoproteins E6 and E7, which disrupt many cellular pathways to drive uncontrolled cell proliferation. One family of proteins targeted by HPV is the Aurora kinase family. Aurora kinases are serine/threonine kinases including Aurora kinase A (AURKA), B (AURKB), and C (AURKC) which are often dysregulated in many cancer types, including HPV driven cancers. All three family members play essential roles in mitotic regulation and accurate cell division.</div><div>The deregulation of Aurora kinases by HPV infection highlights their potential as therapeutic targets in HPV-associated malignancies. Targeting Aurora kinase activity, in combination with current HPV therapies, may provide new avenues for treating HPV-induced cancers and reducing the burden of HPV-related diseases. Combinatorial inhibition targets distinct but overlapping functions of these kinases, thereby reducing the potential for cancer cells to develop resistance. This broad impact emphasizes the capability for Aurora kinase inhibitors not only as anti-mitotic agents but also as modulators of multiple oncogenic pathways. This review explores the combinatorial effects of Aurora kinase inhibition, offering insights into novel therapeutic strategies for the treatment of HPV-driven cancers.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200314"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383935","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}
Pub Date : 2025-06-01Epub Date: 2025-04-17DOI: 10.1016/j.tvr.2025.200318
Said Ali Yerim , Youssef Chami Khazraji , Rachid Bekkali , Maria Bennai , Nassiba Bahra , Imane Chaoui , Fatima Zahra Chellat , Zineb Gaizi , Nabil Tachfouti , Anas Benabdellah , Bouchra Belkadi , Mohammed Attaleb , Mohamed Amine Berraho , Mohammed El Mzibri
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.
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.
{"title":"Evaluating the performance of the Xpert HPV assay in detecting HPV positive cases in Morocco","authors":"Said Ali Yerim , Youssef Chami Khazraji , Rachid Bekkali , Maria Bennai , Nassiba Bahra , Imane Chaoui , Fatima Zahra Chellat , Zineb Gaizi , Nabil Tachfouti , Anas Benabdellah , Bouchra Belkadi , Mohammed Attaleb , Mohamed Amine Berraho , 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":"2025-06-01","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}
Pub Date : 2025-06-01Epub Date: 2025-01-02DOI: 10.1016/j.tvr.2024.200312
Andrea Bilger, Paul F. Lambert
Human cancers are generally thought to develop over the course of decades. Such slow progression is well documented for a variety of cancers that we designate “slow-onset” cancers. “Rapid-onset” cancers, in contrast, can develop in a matter of months in humans or in as little as 9 days in mice. These cancers often develop under conditions that might be expected to accelerate cancer development: early development, immune deficiency, or viral infection. We will discuss rapid-onset cancers in the context of the "hallmarks of cancer" – properties cells must acquire in order to become malignant – focusing on how viruses are particularly well suited to causing rapid-onset cancer.
{"title":"Rapid-onset cancer","authors":"Andrea Bilger, Paul F. Lambert","doi":"10.1016/j.tvr.2024.200312","DOIUrl":"10.1016/j.tvr.2024.200312","url":null,"abstract":"<div><div>Human cancers are generally thought to develop over the course of decades. Such slow progression is well documented for a variety of cancers that we designate “slow-onset” cancers. “Rapid-onset” cancers, in contrast, can develop in a matter of months in humans or in as little as 9 days in mice. These cancers often develop under conditions that might be expected to accelerate cancer development: early development, immune deficiency, or viral infection. We will discuss rapid-onset cancers in the context of the \"hallmarks of cancer\" – properties cells must acquire in order to become malignant – focusing on how viruses are particularly well suited to causing rapid-onset cancer.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200312"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928581","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}
Pub Date : 2025-06-01Epub Date: 2024-12-05DOI: 10.1016/j.tvr.2024.200300
Maya K. Gelbard , Miranda Grace , Annika von Schoeler-Ames , Ida Gnanou , Karl Munger
Human papillomaviruses (HPVs) are a diverse family of viruses with over 450 members that have been identified and fully sequenced. They are classified into five phylogenetic genera: alpha, beta, gamma, mu, and nu. The high-risk alpha HPVs, such as HPV16, have been studied the most extensively due to their medical significance as cancer-causing agents. However, while nearly 70% of all HPVs are members of the gamma genus, they are almost entirely unstudied. This is because gamma HPVs have been considered medically irrelevant commensals as most of them infect the skin and are not known to cause significant clinical lesions in immunocompetent individuals. Members of the gamma 6 HPVs, however, have been detected in the anogenital tract mucosa and HPV101 has been isolated from a premalignant cervical lesion. Moreover, gamma 6 HPVs have a unique genome structure. They lack E6 proteins but in place of E6, they encode unique, small hydrophobic proteins without any close viral or cellular homologs that have been termed E10. Here, we report that HPV101 E7 shares biochemical activities with the high-risk alpha HPV16 E7, including the ability to target the pRB and PTPN14 tumor suppressors for degradation. This study underscores the importance of further characterizing HPV101 and other unstudied HPV species.
{"title":"The HPV101 E7 protein shares host cellular targets and biological activities with high-risk HPV16 E7","authors":"Maya K. Gelbard , Miranda Grace , Annika von Schoeler-Ames , Ida Gnanou , Karl Munger","doi":"10.1016/j.tvr.2024.200300","DOIUrl":"10.1016/j.tvr.2024.200300","url":null,"abstract":"<div><div>Human papillomaviruses (HPVs) are a diverse family of viruses with over 450 members that have been identified and fully sequenced. They are classified into five phylogenetic genera: alpha, beta, gamma, mu, and nu. The high-risk alpha HPVs, such as HPV16, have been studied the most extensively due to their medical significance as cancer-causing agents. However, while nearly 70% of all HPVs are members of the gamma genus, they are almost entirely unstudied. This is because gamma HPVs have been considered medically irrelevant commensals as most of them infect the skin and are not known to cause significant clinical lesions in immunocompetent individuals. Members of the gamma 6 HPVs, however, have been detected in the anogenital tract mucosa and HPV101 has been isolated from a premalignant cervical lesion. Moreover, gamma 6 HPVs have a unique genome structure. They lack E6 proteins but in place of E6, they encode unique, small hydrophobic proteins without any close viral or cellular homologs that have been termed E10. Here, we report that HPV101 E7 shares biochemical activities with the high-risk alpha HPV16 E7, including the ability to target the pRB and PTPN14 tumor suppressors for degradation. This study underscores the importance of further characterizing HPV101 and other unstudied HPV species.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"19 ","pages":"Article 200300"},"PeriodicalIF":4.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792548","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}
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