Tumour Virus Research最新文献_第5页

HPV16 genome structure analysis in oropharyngeal cancer PDXs identifies tumors with integrated and episomal genomes 口咽癌 PDX 中的 HPV16 基因组结构分析确定了具有整合基因组和外显子基因组的肿瘤。

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-06-25 DOI: 10.1016/j.tvr.2024.200285

Claire D. James , Raymonde O. Otoa , Aya H. Youssef , Christian T. Fontan , Malay K. Sannigrahi , Brad Windle , Devraj Basu , Iain M. Morgan

{"title":"HPV16 genome structure analysis in oropharyngeal cancer PDXs identifies tumors with integrated and episomal genomes","authors":"Claire D. James , Raymonde O. Otoa , Aya H. Youssef , Christian T. Fontan , Malay K. Sannigrahi , Brad Windle , Devraj Basu , Iain M. Morgan","doi":"10.1016/j.tvr.2024.200285","DOIUrl":"10.1016/j.tvr.2024.200285","url":null,"abstract":"<div><p>HPV + oropharyngeal squamous cell carcinoma (OPC) incidence recently surpassed cervical cancer and is the most common HPV-related cancer in the developed world. HPV16 is in ∼90 % of HPV + OPCs, with episomal genomes in the majority of cases. Most existing HPV16+ cancer cell lines derive from outside the oropharynx and harbor integrated HPV genomes. Thus, there is need for OPC preclinical models to evaluate standard and experimental therapeutics in the presence of episomal HPV16 oncogenic drivers. Here we characterize HPV genome structures in eight HPV16+ OPC patient-derived xenografts (PDXs), and evaluate their responses to standard chemotherapy. HPV genome state was investigated by combining Southern blot, T5 exonuclease assay, whole genome sequencing, and RNAseq data. This analysis revealed complexity and variation in integrated vs. episomal HPV forms across PDXs and demonstrated that four PDXs predominantly contain episomal HPV16. Episomal status did not ensure favorable <em>in vivo</em> responses to cisplatin therapy, despite the more favorable prognosis previously attributed to episomal HPV + tumors; this could be due to the small number present in the dataset. Our analysis establishes PDX models as test platforms for novel therapies designed to target maintenance of the episomal forms of HPV16 that commonly appear in OPC.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200285"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000090/pdfft?md5=60bb17268635216a165c3c1dae1fc05d&pid=1-s2.0-S2666679024000090-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141472529","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}

引用次数: 0

Editorial board member 编委会成员

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-12-13 DOI: 10.1016/S2666-6790(24)00028-4

引用次数: 0

A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation 人类乳头瘤病毒 16 E2 的新作用：有丝分裂激活 DNA 损伤反应，促进病毒基因组分离。

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-09-07 DOI: 10.1016/j.tvr.2024.200291

Apurva T. Prabhakar , Iain M. Morgan

{"title":"A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation","authors":"Apurva T. Prabhakar , Iain M. Morgan","doi":"10.1016/j.tvr.2024.200291","DOIUrl":"10.1016/j.tvr.2024.200291","url":null,"abstract":"<div><p>Human papillomaviruses (HPV) are causative agents in around 5% of all human cancers. To identify and develop new targeted HPV therapeutics we must enhance our understanding of the viral life cycle and how it interacts with the host. The HPV E2 protein dimerizes and binds to 12bp target sequences in the viral genome and segregates the viral genome during mitosis. In this function, E2 binds to the viral genome and the host chromatin simultaneously, ensuring viral genomes reside in daughter nuclei following cell division. We have demonstrated that a mitotic interaction between E2 and the DNA damage response (DDR) protein TOPBP1 is required for E2 segregation function. In non-infected cells, following DNA damage, TOPBP1 is recruited to the mitotic host genome via interaction with MDC1 and this interaction protects DNA integrity during mitosis. Recently we demonstrated that the E2-TOPBP1 interaction activates the DNA damage response (DDR) during mitosis independently from external stimuli, promoting TOPBP1 interaction with mitotic chromatin and therefore segregation of the viral genome. Therefore, the virus has hijacked an existing host mechanism in order to segregate the viral genome. This intricate E2 function will be described and discussed.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200291"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000156/pdfft?md5=dc35edad86e9980ce61707e0d71568ab&pid=1-s2.0-S2666679024000156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156640","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}

引用次数: 0

Modulation of connexin 43 in viral infections 在病毒感染中调节连接蛋白 43

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-11-08 DOI: 10.1016/j.tvr.2024.200296

Harry Scott , Patricia E. Martin , Sheila V. Graham

引用次数: 0

Opportunities to advance cervical cancer prevention and care 推进宫颈癌预防和护理的机遇

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1016/j.tvr.2024.200292

Grant Brooke , Sebastian Wendel , Abhineet Banerjee , Nicholas Wallace

引用次数: 0

Modulation of epithelial homeostasis by HPV using Notch and Wnt 人乳头瘤病毒利用 Notch 和 Wnt 调节上皮细胞的稳态。

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-11-13 DOI: 10.1016/j.tvr.2024.200297

June See Chong, John Doorbar

引用次数: 0

The imprint of viral oncoproteins on the variable clinical behavior among human papilloma virus-related oropharyngeal squamous cell carcinomas 病毒癌蛋白对人类乳头瘤病毒相关口咽鳞状细胞癌不同临床表现的影响。

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-11-01 DOI: 10.1016/j.tvr.2024.200295

Malay K. Sannigrahi , Lovely Raghav , Ahmed Diab , Devraj Basu

{"title":"The imprint of viral oncoproteins on the variable clinical behavior among human papilloma virus-related oropharyngeal squamous cell carcinomas","authors":"Malay K. Sannigrahi , Lovely Raghav , Ahmed Diab , Devraj Basu","doi":"10.1016/j.tvr.2024.200295","DOIUrl":"10.1016/j.tvr.2024.200295","url":null,"abstract":"<div><div>Human papilloma virus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) are variable in their progression, immune landscape, treatment responses, and clinical outcomes. Their behavior is impacted not only by differences in host genomic alterations but also by diversity in levels and activity of HPV-encoded oncoproteins. Striking differences in HPV mRNA levels are found among HPV+ OPSCCs and likely derive in part from variations in the structurally diverse mix of integrated and episomal HPV genomes they often contain. Viral oncoprotein levels and function are also impacted by differential splicing of the two long polycistronic transcripts of HPV16, the HPV type within most HPV+ OPSCCs. Further variation in viral oncoprotein function arises from the distinct lineages and sub-lineages of HPV16, which encode polymorphisms in functionally important portions of oncogenes. Here we review the limited current knowledge linking HPV mRNA expression and splicing to differences in oncoprotein function that likely influence OPSCC behavior. We also summarize the evolving understanding of HPV16 physical genome state and genetic variants and their potential contributions to HPV oncoprotein levels and function. Addressing considerable remaining challenges in defining the quantitative and qualitative imprint of HPV oncoproteins on each OPSCC holds promise to guide personalization of therapy for this disease.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200295"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570074","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}

引用次数: 0

HBx integration in diffuse large B-cell lymphoma inhibits Caspase-3-PARP related apoptosis 弥漫大 B 细胞淋巴瘤中的 HBx 整合可抑制与 Caspase-3-PARP 相关的细胞凋亡。

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-07-18 DOI: 10.1016/j.tvr.2024.200290

Yanchun Wang , Xiaolin Guan , Fangfang Lv , Yi Rong , Xin Meng , Ying Tong , Xiaolu Ma , Hui Zheng , Cuncun Chen , Suhong Xie , Heng Zhang , Feng Dong , Lin Guo , Renquan Lu

{"title":"HBx integration in diffuse large B-cell lymphoma inhibits Caspase-3-PARP related apoptosis","authors":"Yanchun Wang , Xiaolin Guan , Fangfang Lv , Yi Rong , Xin Meng , Ying Tong , Xiaolu Ma , Hui Zheng , Cuncun Chen , Suhong Xie , Heng Zhang , Feng Dong , Lin Guo , Renquan Lu","doi":"10.1016/j.tvr.2024.200290","DOIUrl":"10.1016/j.tvr.2024.200290","url":null,"abstract":"<div><p>Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and <em>hepatitis B X</em> (<em>HBx</em>) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of <em>HBx</em> integration in DLBCL. The data showed that clinical DLBCL cells demonstrated <em>HBx</em> integration, and the sequencing analysis of integrated sites validated <em>HBx</em> integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the <em>HBx</em>-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the <em>HBx</em>-negative samples. Therefore, <em>HBx</em> integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200290"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000144/pdfft?md5=3ffb604d2a76191481057e06101dce0d&pid=1-s2.0-S2666679024000144-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735646","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}

引用次数: 0

A peptide derived from sorting nexin 1 inhibits HPV16 entry, retrograde trafficking, and L2 membrane spanning 一种从分拣奈克辛 1 提取的多肽可抑制 HPV16 的进入、逆行运输和 L2 膜跨越。

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-06-21 DOI: 10.1016/j.tvr.2024.200287

Shuaizhi Li , Zachary L. Williamson , Matthew A. Christofferson , Advait Jeevanandam , Samuel K. Campos

{"title":"A peptide derived from sorting nexin 1 inhibits HPV16 entry, retrograde trafficking, and L2 membrane spanning","authors":"Shuaizhi Li , Zachary L. Williamson , Matthew A. Christofferson , Advait Jeevanandam , Samuel K. Campos","doi":"10.1016/j.tvr.2024.200287","DOIUrl":"10.1016/j.tvr.2024.200287","url":null,"abstract":"<div><p>High risk human papillomavirus (HPV) infection is responsible for 99 % of cervical cancers and 5 % of all human cancers worldwide. HPV infection requires the viral genome (vDNA) to gain access to nuclei of basal keratinocytes of epithelium. After virion endocytosis, the minor capsid protein L2 dictates the subcellular retrograde trafficking and nuclear localization of the vDNA during mitosis. Prior work identified a cell-permeable peptide termed SNX1.3, derived from the BAR domain of sorting nexin 1 (SNX1), that potently blocks the retrograde and nuclear trafficking of EGFR in triple negative breast cancer cells. Given the importance of EGFR and retrograde trafficking pathways in HPV16 infection, we set forth to study the effects of SNX1.3 within this context. SNX1.3 inhibited HPV16 infection by both delaying virion endocytosis, as well as potently blocking virion retrograde trafficking and Golgi localization. SNX1.3 had no effect on cell proliferation, nor did it affect post-Golgi trafficking of HPV16. Looking more directly at L2 function, SNX1.3 was found to impair membrane spanning of the minor capsid protein. Future work will focus on mechanistic studies of SNX1.3 inhibition, and the role of EGFR signaling and SNX1-mediated endosomal tubulation, cargo sorting, and retrograde trafficking in HPV infection.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200287"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000119/pdfft?md5=1250a168dc79de16a0d68ff0fe70f4a3&pid=1-s2.0-S2666679024000119-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443749","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}

引用次数: 0

Genomic diversity of HPV6 and HPV11 in recurrent respiratory papillomatosis: Association with malignant transformation in the lungs and clinical outcomes 复发性呼吸道乳头状瘤病中 HPV6 和 HPV11 的基因组多样性：与肺部恶性转化和临床结果的关系

IF 4.7

Tumour Virus Research Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI: 10.1016/j.tvr.2024.200294

Massilva Rahmoun , Audrey Aussel , Sarah Bouzidi , Vincent Pedergnana , Victor Malassigné , Julien Puech , David Veyer , Hélène Péré , Charles Lepine , Fabian Blanc , Nathalie Boulle , Valérie Costes-Martineau , Ignacio G. Bravo

{"title":"Genomic diversity of HPV6 and HPV11 in recurrent respiratory papillomatosis: Association with malignant transformation in the lungs and clinical outcomes","authors":"Massilva Rahmoun , Audrey Aussel , Sarah Bouzidi , Vincent Pedergnana , Victor Malassigné , Julien Puech , David Veyer , Hélène Péré , Charles Lepine , Fabian Blanc , Nathalie Boulle , Valérie Costes-Martineau , Ignacio G. Bravo","doi":"10.1016/j.tvr.2024.200294","DOIUrl":"10.1016/j.tvr.2024.200294","url":null,"abstract":"<div><div>Recurrent respiratory papillomatosis (RRP) is a rare, proliferative disease caused by human papillomavirus 6 (HPV6) and HPV11. RRP can occasionally spread and undergo malignant transformation.</div><div>We analysed samples across time for five RRP patients with malignant transformation and four with highly recurrent, non-malignant RRP by applying high-throughput sequencing.</div><div>Patients with malignant transformation were infected by HPV11_A1/A2, while most non-malignant cases were associated with HPV6. Transient multiple infections with HPV6 and HPV11 were found in two patients, and resolved later to single infections. Viral genome loads were homogeneous across groups (median = 78 viral genomes per human genome). Within-patient, we did not observe differences between the viral sequences in the papillomatous lesions and in the malignant tissue. Genetic analysis of the <em>NLRP1</em> gene revealed no known mutations linked to idiopathic RRP, though some novel variants merit to be explored in larger cohorts.</div><div>HPV11 infections appear associated with RRP malignant transformation in young patients. Multiple infections can occur in RRP, but within-patient viral diversity is minimal for a given genotype. Our results confirm the importance of viral genotype in disease prognosis and are consistent with growing evidence of HPV11 infections to be differentially associated with RRP malignant transformation in young patients.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200294"},"PeriodicalIF":4.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555630","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}

引用次数: 0