Tumour Virus Research最新文献

{"title":"JC Virus Small Tumor Antigen Promotes S Phase Entry and Cell Cycle Progression.","authors":"Renato Biffi, Stefanie W Benoit, Ilker K Sariyer, Mahmut Safak","doi":"10.1016/j.tvr.2024.200298","DOIUrl":"https://doi.org/10.1016/j.tvr.2024.200298","url":null,"abstract":"<p><p>The early coding region of JC virus (JCV) encodes several regulatory proteins including large T antigen (LT-Ag), small t antigen (Sm t-Ag) and T' proteins because of the alternative splicing of the pre-mRNA. LT-Ag plays a critical role in cell transformation by targeting the key cell cycle regulatory proteins including p53 and pRb, however, the role of Sm t-Ag in this process remains elusive. Here, we investigated the effect of Sm t-Ag on the cell cycle progression and demonstrated that it facilitates S phase entry and exit when cells are released from G0/G1 growth arrest. Examination of the cell cycle stage specific expression profiles of the selected cyclins and cyclin-dependent kinases, including those active at the G1/S and G2/M transition state, demonstrated a higher level of early expression of these regulators such as cyclin B, cycling E, and Cdk2. In addition, analysis of the effect of Sm t-Ag on the growth promoting pathways including those active in the PI3K/Akt/mTOR axis showed substantially higher levels of the phosphorylated-Akt, -Gsk3-β and -S6K1 in Sm t-Ag-positive cells. Collectively, our results demonstrate that Sm t-Ag promotes cell cycle progression by activating the growth promoting pathways through which it may contribute to LT-Ag-mediated cell transformation.</p>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":" ","pages":"200298"},"PeriodicalIF":4.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717194","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":"Modulation of epithelial homeostasis by HPV using Notch and Wnt","authors":"June See Chong,&nbsp;John Doorbar","doi":"10.1016/j.tvr.2024.200297","DOIUrl":"10.1016/j.tvr.2024.200297","url":null,"abstract":"<div><div>Highly conserved signalling pathways such as Notch and Wnt are essential in the regulation of differentiation and proliferation processes during adult tissue homeostasis. Human papillomaviruses (HPVs) have evolved with humans to manipulate these signalling pathways to establish a basal reservoir of infected cells by limiting HPV-infected keratinocyte differentiation whilst ensuring that differentiating cells are in a replication-competent state. Here, we focus on the canonical Notch and Wnt signalling pathways and their crosstalk to ensure cell-fate lineage determination during epithelial homeostasis. We then examine how HPVs use their E6 and E7 proteins to inhibit differentiation and maintain stem-like characteristics using Notch and Wnt in HPV-infected cells. Determining the functions of E6 and E7 in the maintenance of the infected cell reservoir, and the molecular crosstalk between Notch and Wnt is vital for our understanding of HPV persistence, and may represent an important factor in the development of therapeutic agents for HPV-associated disease.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200297"},"PeriodicalIF":4.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632421","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":"Modulation of connexin 43 in viral infections","authors":"Harry Scott ,&nbsp;Patricia E. Martin ,&nbsp;Sheila V. Graham","doi":"10.1016/j.tvr.2024.200296","DOIUrl":"10.1016/j.tvr.2024.200296","url":null,"abstract":"<div><div>Connexins are essential for intercellular communication through gap junctions and the maintenance of cellular and tissue homeostasis. Connexin 43 (Cx43) is the most ubiquitously expressed connexin. As well as regulating homeostasis, Cx43 hemichannels and gap junctions play important roles in inflammation and the immune response. This, coupled with a range of non-channel functions performed by Cx43 makes it an attractive target for viruses. Recently, several groups have begun to explore the relationship between Cx43 and viral infection, with a diverse array of viruses being found to alter Cx43 hemichannels/gap junctions. Importantly, this includes several small DNA tumour viruses, which may target Cx43 to promote tumorigenesis. This review focuses on the ability of selected RNA/DNA viruses and retroviruses to either positively or negatively regulate Cx43 hemichannels and gap junctions in order to carry out their lifecycles. The role of Cx43 regulation by tumour viruses is also discussed in relation to tumour progression.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200296"},"PeriodicalIF":4.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632420","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":"The imprint of viral oncoproteins on the variable clinical behavior among human papilloma virus-related oropharyngeal squamous cell carcinomas","authors":"Malay K. Sannigrahi ,&nbsp;Lovely Raghav ,&nbsp;Ahmed Diab ,&nbsp;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":"2024-11-01","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}

{"title":"Genomic diversity of HPV6 and HPV11 in recurrent respiratory papillomatosis: Association with malignant transformation in the lungs and clinical outcomes","authors":"Massilva Rahmoun ,&nbsp;Audrey Aussel ,&nbsp;Sarah Bouzidi ,&nbsp;Vincent Pedergnana ,&nbsp;Victor Malassigné ,&nbsp;Julien Puech ,&nbsp;David Veyer ,&nbsp;Hélène Péré ,&nbsp;Charles Lepine ,&nbsp;Fabian Blanc ,&nbsp;Nathalie Boulle ,&nbsp;Valérie Costes-Martineau ,&nbsp;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":"2024-10-29","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}

{"title":"The SV40 virus enhancer functions as a somatic hypermutation-targeting element with potential tumorigenic activity","authors":"Filip Šenigl ,&nbsp;Anni I. Soikkeli ,&nbsp;Salomé Prost ,&nbsp;David G. Schatz ,&nbsp;Martina Slavková ,&nbsp;Jiří Hejnar ,&nbsp;Jukka Alinikula","doi":"10.1016/j.tvr.2024.200293","DOIUrl":"10.1016/j.tvr.2024.200293","url":null,"abstract":"<div><div>Simian virus 40 (SV40) is a monkey virus with tumorigenic potential in rodents and is associated with several types of human cancers, including lymphomas. A related Merkel cell polyomavirus causes carcinoma in humans by expressing truncated large tumor antigen (LT), with truncations caused by APOBEC family of cytidine deaminase-induced mutations. AID (activation-induced cytidine deaminase), a member of the APOBEC family, is the initiator of the antibody diversification process known as somatic hypermutation and its aberrant expression and targeting is a frequent source of lymphomagenesis. In this study, we investigated whether AID could cause mutations in SV40 <em>LT</em>. We demonstrate that the SV40 enhancer has strong somatic hypermutation targeting activity in several cell types and that AID-induced mutations accumulate in SV40 <em>LT</em> in B cells and kidney cells and cause truncated LT expression in B cells. Our results argue that the ability of the SV40 enhancer to target somatic hypermutation to <em>LT</em> is a potential source of LT truncation events that could contribute to tumorigenesis in various cell types, thereby linking SV40 infection with malignant development through a novel mutagenic pathway.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200293"},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560626","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":"Opportunities to advance cervical cancer prevention and care","authors":"Grant Brooke ,&nbsp;Sebastian Wendel ,&nbsp;Abhineet Banerjee ,&nbsp;Nicholas Wallace","doi":"10.1016/j.tvr.2024.200292","DOIUrl":"10.1016/j.tvr.2024.200292","url":null,"abstract":"<div><div>Cervical cancer (CaCx) is a major public health issue, with over 600,000 women diagnosed annually. CaCx kills someone every 90 s, mostly in low- and middle-income countries. There are effective yet imperfect mechanisms to prevent CaCx. Since human papillomavirus (HPV) infections cause most CaCx, they can be prevented by vaccination. Screening methodologies can identify premalignant lesions and allow interventions before a CaCx develops. However, these tools are less feasible in resource-poor environments. Additionally, current screening modalities cannot triage lesions based on their relative risk of progression, which results in overtreatment. CaCx care relies heavily on genotoxic agents that cause severe side effects. This review discusses ways that recent technological advancements could be leveraged to improve CaCx care and prevention.</div></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200292"},"PeriodicalIF":4.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560627","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":"A new role for human papillomavirus 16 E2: Mitotic activation of the DNA damage response to promote viral genome segregation","authors":"Apurva T. Prabhakar ,&nbsp;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":"2024-09-07","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}

{"title":"HBx integration in diffuse large B-cell lymphoma inhibits Caspase-3-PARP related apoptosis","authors":"Yanchun Wang ,&nbsp;Xiaolin Guan ,&nbsp;Fangfang Lv ,&nbsp;Yi Rong ,&nbsp;Xin Meng ,&nbsp;Ying Tong ,&nbsp;Xiaolu Ma ,&nbsp;Hui Zheng ,&nbsp;Cuncun Chen ,&nbsp;Suhong Xie ,&nbsp;Heng Zhang ,&nbsp;Feng Dong ,&nbsp;Lin Guo ,&nbsp;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":"2024-07-18","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}

{"title":"The impact of DNA tumor viruses in low-to-middle income countries (LMICS): A literature review","authors":"","doi":"10.1016/j.tvr.2024.200289","DOIUrl":"10.1016/j.tvr.2024.200289","url":null,"abstract":"<div><p>DNA viruses are common in the human population and act as aetiological agents of cancer on a large scale globally. They include the human papillomaviruses (HPV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis viruses, and human polyomaviruses. Oncogenic viruses employ different mechanisms to induce cancer. Notably, cancer only develops in a minority of individuals who are infected, usually following protracted years of chronic infection. The human papillomaviruses (HPVs) are associated with the highest number of cancer cases, including cervical cancer and other epithelial malignancies. Hepatitis B virus (HBV) and the RNA virus hepatitis C (HCV) are significant contributors to hepatocellular cancer (HCC). Other oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). The identification of these infectious agents as aetiological agents for cancer has led to reductions in cancer incidence through preventive interventions such as HBV and HPV vaccination, HPV-DNA based cervical cancer screening, antiviral treatments for chronic HBV and HCV infections, and screening of blood for transfusion for HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may provide further understanding of the aetiology and development of cancer, and novel approaches for prevention and treatment. Cervical cancer, caused by HPV, is the leading gynaecological malignancy in LMICs, with high age-standardised incidence and mortality rates, HCC due to HBV is an important cause of cancer deaths, and the burden of other cancer attributable to infections continues to rise globally. Hence, cancers attributable to DNA viruses have become a significant global health challenge. These viruses hence warrant continued attention and interrogation as efforts to understand them further and device further preventive interventions are critical.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200289"},"PeriodicalIF":4.7,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000132/pdfft?md5=80e4f481a18359eac895e3e2cb06f042&pid=1-s2.0-S2666679024000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560346","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}