Man Teng , Jun Luo , Yaoyao Zhang , Vishwanatha R.A.P. Reddy , Priya Samuel , Yongxiu Yao , Venugopal Nair
{"title":"Viral miRNA delivered by exosomes from Marek's disease virus-transformed lymphoma cell line exerts regulatory function in internalized primary chicken embryo fibroblast cells","authors":"Man Teng , Jun Luo , Yaoyao Zhang , Vishwanatha R.A.P. Reddy , Priya Samuel , Yongxiu Yao , Venugopal Nair","doi":"10.1016/j.tvr.2024.200286","DOIUrl":"10.1016/j.tvr.2024.200286","url":null,"abstract":"<div><p>In the past decade, research has demonstrated that viral miRNAs encoded by a number of viral genomes, particularly by most of the herpesvirus including Marek's disease virus (MDV), play important regulatory roles in viral infection, replication, and regulation of tumorigenesis. As macrovesicles in cells, exosomes can deliver viral miRNAs and exert gene regulatory functions. Whether the exosomes play a role in the replication, pathogenesis/tumorigenesis of avian herpesviruses such as oncogenic Marek's disease virus (MDV) remains unclear. Herein we extracted and identified the exosomes from MDV-transformed T cell line MSB-1 and demonstrated high abundance of MDV-1 miRNA expression. Using dual luciferase-based reporter assay, we also demonstrated that the exosomes derived from MSB-1 can deliver functional miRNA successfully into primary chicken embryo fibroblasts. These findings provide new insights into the role of exosomes and the mechanisms of how virus-encoded miRNA function in MDV latency/activation switching, viral replication, pathogenesis and/or tumorigenesis.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"18 ","pages":"Article 200286"},"PeriodicalIF":4.7,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000107/pdfft?md5=366a07b88654841625509288d1263f73&pid=1-s2.0-S2666679024000107-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447592","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}
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":"2024-06-21","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}
{"title":"Cervical cytology and HPV distribution in Cape Verde: A snapshot of a country taken during its first HPV nation-wide vaccination campaign","authors":"Rita Vieira , Diana Montezuma , Carla Barbosa , Isabel Macedo Pinto","doi":"10.1016/j.tvr.2024.200280","DOIUrl":"10.1016/j.tvr.2024.200280","url":null,"abstract":"<div><p>Cervical cancer ranks as the third most common female cancer in Cape Verde and is the leading cause of cancer-related deaths among women in the country. While Human Papillomavirus (HPV) vaccination, which started in 2021, is anticipated to significantly reduce disease incidence, cervical screening remains crucial for non-vaccinated women. We retrospectively reviewed gynecologic cytology exams and HPV tests performed in Cape Verde between 2017 and April 2023 and processed at IMP Diagnostics. For this study, we considered 13035 women with cytology examinations performed and, 2013 of these, also with an HPV molecular test. Cytology diagnostics comprised 83 % NILM cases; 12 % ASC-US; 2.7 % LSIL; 1.2 % ASC-H; 0.5 % HSIL and 0.1 % SCC. In 505 (25.1 %) high-risk HPV infection was detected. Prevalence of HPV infection varied with age, peaking at young ages - ≤24 years old (55.5 %) and 25-35-year-old women (31.5 %) - and the lowest after 66 years old (9.7 %). Herein we present a comprehensive study regarding Cape Verde's cervical cytology and HPV distribution, aiming to provide a snapshot of the country's cervical cytology results and HPV distribution in recent years. Moreover, these data may contribute to establish a baseline to assess, in the future, the vaccination impact in the country.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"17 ","pages":"Article 200280"},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000041/pdfft?md5=64eb631123fa06b8823a59b3dee4cc51&pid=1-s2.0-S2666679024000041-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871204","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}
Charles Lepine , Nicolas Leboulanger , Cécile Badoual
{"title":"Juvenile onset recurrent respiratory papillomatosis: What do we know in 2024 ?","authors":"Charles Lepine , Nicolas Leboulanger , Cécile Badoual","doi":"10.1016/j.tvr.2024.200281","DOIUrl":"https://doi.org/10.1016/j.tvr.2024.200281","url":null,"abstract":"<div><p>Juvenile onset recurrent respiratory papillomatosis is a lifelong benign squamous lesion associated with HPV infection, particularly HPV6 and HPV11 genotypes. These lesions are rare, but can lead to laryngeal obturations, which can cause disabling dyspnea, or transform into squamous cell carcinoma. The aim here is to provide an epidemiological, biological and clinical overview of this pathology, particularly in children, in order to understand the issues at stake in terms of research and the development of medical and therapeutic management tools.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"17 ","pages":"Article 200281"},"PeriodicalIF":4.3,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000053/pdfft?md5=b93f2e4869c9a623105e0c8d405d110b&pid=1-s2.0-S2666679024000053-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140823868","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}
Oscar Trejo-Cerro , Om Basukala , Michael P. Myers , Lawrence Banks
{"title":"HPV16 E7 modulates the cell surface expression of MET and CD109 via the AP2 complex","authors":"Oscar Trejo-Cerro , Om Basukala , Michael P. Myers , Lawrence Banks","doi":"10.1016/j.tvr.2024.200279","DOIUrl":"10.1016/j.tvr.2024.200279","url":null,"abstract":"<div><p>Multiple cellular pathways are affected by HPV E6 and E7 oncoproteins, including endocytic and cellular trafficking. HPV-16 E7 can target the adaptor protein (AP) complex, which contains proteins important during endocytosis transport. To further investigate the role of HPV E7 during this process, we analysed the expression of cell surface proteins in NIKS cells expressing HPV-16 E7. We show that different cell surface proteins are regulated by HPV-16 E7 via interaction with AP2. We observed that the expression of MET and CD109 membrane protein seems to be upregulated in cells expressing E7. Moreover, the interaction of MET and CD109 with AP2 proteins is disrupted by HPV-16 E7. In addition, in the absence of HPV-16 E7, there is a downregulation of the cell membrane expression of MET and CD109 in HPV-positive cell lines. These results expand our knowledge of the functions of E7 and open new potential cellular pathways affected by this oncoprotein.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"17 ","pages":"Article 200279"},"PeriodicalIF":4.3,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266667902400003X/pdfft?md5=7080733ec5725ed90815ab591a98a958&pid=1-s2.0-S266667902400003X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133170","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":"Surveillance of human papillomavirus through salivary diagnostics - A roadmap to early detection of oropharyngeal cancer men","authors":"Akila Wijesekera , Chameera Ekanayake Weeramange , Sarju Vasani , Liz Kenny , Emma Knowland , Jayampath Seneviratne , Chamindie Punyadeera","doi":"10.1016/j.tvr.2024.200278","DOIUrl":"10.1016/j.tvr.2024.200278","url":null,"abstract":"<div><p>Human papillomavirus (HPV) is the most common sexually transmitted disease. Certain strains have the potential to cause malignancy in multiple anatomical sites if not cleared by the immune system. In most infected people, HPV is cleared within two years. However, HPV may persist in susceptible individuals with certain risk factors, eventually leading to malignancy. New evidence suggests that over 75% of all oropharyngeal cancers (OPC) are directly attributable to HPV. It is estimated that prophylactic HPV vaccination alone may take at least 25 years to have a significant impact on reducing the incidence of OPC. The temporal link between detection of oral HPV, persistence of the infection and the subsequent development of OPC have been well established. Moreover, men have threefold higher risk than women for acquiring HPV-OPC. This comprehensive review focuses on OPC development in men, highlighting the risk factors associated with malignant transformation of HPV-OPC. Current evidence is insufficient to determine whether early identification of at-risk demographics, screening, and prompt diagnosis result in improved outcomes. Hitherto, the effectiveness of an oral HPV screening program in this regard has not been investigated. Nevertheless, the potential to emulate the success of the cervical screening program remains a very real possibility.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"17 ","pages":"Article 200278"},"PeriodicalIF":4.3,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000028/pdfft?md5=5d8c4900240ff112522756ab200f6d35&pid=1-s2.0-S2666679024000028-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040875","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":"E4orf1: The triple agent of adenovirus – Unraveling its roles in oncogenesis, infectious obesity and immune responses in virus replication and vector therapy","authors":"Lilian Göttig , Sabrina Schreiner","doi":"10.1016/j.tvr.2024.200277","DOIUrl":"10.1016/j.tvr.2024.200277","url":null,"abstract":"<div><p>Human Adenoviruses (HAdV) are nearly ubiquitous pathogens comprising numerous sub-types that infect various tissues and organs. Among many encoded proteins that facilitate viral replication and subversion of host cellular processes, the viral E4orf1 protein has emerged as an intriguing yet under-investigated player in the complex interplay between the virus and its host. E4orf1 has gained attention as a metabolism activator and oncogenic agent, while recent research is showing that E4orf1 may play a more important role in modulating cellular pathways such as PI3K-Akt-mTOR, Ras, the immune response and further HAdV replication stages than previously anticipated.</p><p>In this review, we aim to explore the structure, molecular mechanisms, and biological functions of E4orf1, shedding light on its potentially multifaceted roles during HAdV infection, including metabolic diseases and oncogenesis. Furthermore, we discuss the role of functional E4orf1 in biotechnological applications such as Adenovirus (AdV) vaccine vectors and oncolytic AdV. By dissecting the intricate relationships between HAdV types and E4orf1 proteins, this review provides valuable insights into viral pathogenesis and points to promising areas of future research.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"17 ","pages":"Article 200277"},"PeriodicalIF":4.3,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679024000016/pdfft?md5=c1289e68488a5387087db9e3293fa36e&pid=1-s2.0-S2666679024000016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013742","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}
Kirsten Rozemeijer , Fernando Dias Gonçalves Lima , Timo J. ter Braak , Albertus T. Hesselink , Jan M. Prins , Henry J.C. de Vries , Renske D.M. Steenbergen
{"title":"Analytical validation and diagnostic performance of the ASCL1/ZNF582 methylation test for detection of high-grade anal intraepithelial neoplasia and anal cancer","authors":"Kirsten Rozemeijer , Fernando Dias Gonçalves Lima , Timo J. ter Braak , Albertus T. Hesselink , Jan M. Prins , Henry J.C. de Vries , Renske D.M. Steenbergen","doi":"10.1016/j.tvr.2023.200275","DOIUrl":"10.1016/j.tvr.2023.200275","url":null,"abstract":"<div><p>DNA methylation testing on biopsies can detect high-grade anal intraepithelial neoplasia (HGAIN) in need of treatment and anal cancer. This study aimed to analytically validate and determine the diagnostic performance of a newly developed multiplex quantitative methylation-specific PCR, PreCursor-M AnoGYN (RUO), combining <em>ASCL1, ZNF582</em> and a reference (<em>ACTB</em>) in one assay. Analytical validation was performed on two qPCR devices using predefined quality criteria. Diagnostic performance was determined on a cross-sectional series of 111 anal biopsies covering all stages of anal disease. Differences in methylation levels were assessed using the Kruskal-Wallis test. Area under the curve was determined using logistic regression analysis. Detection rates were calculated at predefined specificities for the cross-sectional and an additional longitudinal series of 23 HGAIN biopsies preceding anal cancer (i.e., progressive HGAIN).</p><p>For both devices analytical quality criteria were met. <em>ASCL1</em> and <em>ZNF582</em> methylation levels increased with increasing severity of disease (<em>p < 6*10</em><sup><em>−8</em></sup>). Diagnostic performance for AIN3<sup>+</sup> was 0.81. All cancers and virtually all progressive HGAIN were detected at 70% and 80% specificity.</p><p>In conclusion, the <em>ASCL1/ZNF582</em> methylation test (PreCursor-M AnoGYN (RUO)) was demonstrated to be highly robust and reproducible. Moreover, it had excellent diagnostic accuracy to detect AIN3<sup>+</sup> and can potentially be used to guide HGAIN management.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"17 ","pages":"Article 200275"},"PeriodicalIF":4.3,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666679023000228/pdfft?md5=c19dacaf0f34ae20fdc44257cf56f0c3&pid=1-s2.0-S2666679023000228-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075780","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}
Brunno Felipe Ramos Caetano , Viviana Loureiro Rocha , Bruno Cesar Rossini , Lucilene Delazari Dos Santos , Deilson Elgui De Oliveira
{"title":"Epstein-Barr Virus miR-BARTs 7 and 9 modulate viral cycle, cell proliferation, and proteomic profiles in Burkitt lymphoma","authors":"Brunno Felipe Ramos Caetano , Viviana Loureiro Rocha , Bruno Cesar Rossini , Lucilene Delazari Dos Santos , Deilson Elgui De Oliveira","doi":"10.1016/j.tvr.2023.200276","DOIUrl":"10.1016/j.tvr.2023.200276","url":null,"abstract":"<div><p>The Epstein-Barr Virus (EBV) encodes viral microRNAs (miRs) that have been implicated in the pathogenesis of nasopharyngeal and gastric carcinomas, yet their potential roles in lymphomas remain to be fully elucidated. This study evaluated the impact of CRISPR/Cas9-mediated knockdown of EBV miRs BART-7 and BART-9 in EBV-positive Burkitt lymphoma cells Akata. As anticipated, the Akata cells subjected to CRISPR/Cas9-mediated knockdown of either EBV BART-7 or BART-9 exhibited a significant reduction in the expression of these viral miRs compared to cells with wild-type (wt) EBV genomes. This outcome effectively validates the experimental model employed in this study. Knocking down either BART-7 or BART-9 resulted in a notable reduction in cell viability and proliferation rates, alongside an elevation in the expression of EBV lytic genes. Global proteomic analysis revealed that the knockdown of EBV BART-7 significantly decreased the expression of ubiquitin/proteasome proteins while concurrently increasing RNA binding proteins (RBPs). Conversely, BART-9 knockdown reduced proteins associated with oxidoreductase activity, particularly those involved in fatty acid metabolism. Our findings unveil previously undiscovered EBV miRs BARTs 7 and 9 roles in cellular pathways relevant to both viral biology and lymphomagenesis.</p></div>","PeriodicalId":52381,"journal":{"name":"Tumour Virus Research","volume":"17 ","pages":"Article 200276"},"PeriodicalIF":4.3,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266667902300023X/pdfft?md5=316875d8e9bcf16995d37e8248320697&pid=1-s2.0-S266667902300023X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075781","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}