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Viruses
Special Issues
Recent Progress in Tumor Virology Research
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Recent Progress in Tumor Virology Research

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 44072

Special Issue Editors

Dr. Subhash C. Verma

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Guest Editor
Department of Microbiology & Immunology, University of Nevada, Reno School of Medicine, 1664 North Virginia Street, MS 320, Center for Molecular Medicine, 211F, Reno, NV 89557, USA
Interests: herpesvirology; latency and viral reactivation; genetic and epigenetic factors of viral replication; zika virus pathogenesis
Special Issues, Collections and Topics in MDPI journals
Dr. Sherif T. S. Hassan

E-Mail Website
Guest Editor
Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00 Prague, Czech Republic
Interests: infectious diseases; pharmacology and toxicology of natural products; analytical methods for isolation and identification of natural products; molecular mechanisms of pharmacological action; pediatric infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In 1966, the Nobel Prize in Physiology or Medicine was awarded for the discovery of tumor-inducing viruses, since then,  tumor viruses studies have guided us to significant findings in cancer research, including the discovery of various oncoproteins, as well as tumor suppressor proteins that regulate the development of various types of cancer. It has been estimated that viruses trigger approximately 15% of all human cancers, and hence, extensive studies have been performed on tumor viruses to get more insights into the role of viruses in the development of cancer. Several viruses are known to induce human tumors. For instance, human papillomavirus (HPV) accounted for the major global cancer burden, generating up 5.2% of infection-associated cancers, while Kaposi’s sarcoma-associated herpesvirus (KSHV) and Merkel cell polyomavirus (MCV) have recently been identified as causative agents in Merkel cell carcinomas (MCC).

In this Special Issue, we encourage the submission of manuscripts that cover recent advances in tumor virology research with an emphasis on the following areas:

  • Identification of new cancer pathways targeted by tumor viruses;
  • Identification of novel biomarkers for viral tumors;
  • Identification of novel therapeutic targets/agents for viral cancer and development of new anticancer virus-based treatments;
  • Identification of new tumor-inducing viruses.
Dr. Subhash C. Verma
Dr. Sherif T. S. Hassan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Tumor-inducing viruses
  • Viral oncology
  • Viral markers
  • Viral therapeutics
  • Virus-encoded antigen
  • Viral tumorigenesis
  • Carcinogenesis
  • Cancer development
  • Virus discovery

Published Papers (13 papers)

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Editorial

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3 pages, 185 KiB  
Editorial
Tumor Viruses and Their Associated Cancers: Remain on the Track with the Latest Advances
by Sherif T. S. Hassan
Viruses 2022, 14(2), 262; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020262 - 27 Jan 2022
Viewed by 1920
Abstract
Infection with certain types of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) viruses, known as tumor viruses or oncogenic viruses, can lead to cancer [...] Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)

Research

Jump to: Editorial, Review, Other

14 pages, 1483 KiB  
Article
Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein–Barr Virus in Classical Hodgkin Lymphoma
by Antonio Santisteban-Espejo, Jose Perez-Requena, Lidia Atienza-Cuevas, Julia Moran-Sanchez, Maria del Carmen Fernandez-Valle, Irene Bernal-Florindo, Raquel Romero-Garcia and Marcial Garcia-Rojo
Viruses 2021, 13(12), 2523; https://0-doi-org.brum.beds.ac.uk/10.3390/v13122523 - 15 Dec 2021
Cited by 6 | Viewed by 2236
Abstract
The prognostic impact of the presence of Epstein–Barr virus (EBV) in classical Hodgkin lymphoma (cHL) is controversial. Previous studies reported heterogeneous results, rendering difficult the clinical validation of EBV as a prognostic biomarker in this lymphoma. The objective of this study was to [...] Read more.
The prognostic impact of the presence of Epstein–Barr virus (EBV) in classical Hodgkin lymphoma (cHL) is controversial. Previous studies reported heterogeneous results, rendering difficult the clinical validation of EBV as a prognostic biomarker in this lymphoma. The objective of this study was to evaluate the survival impact of the expression of EBV Latent-Membrane Protein 1 (EBV-LMP1) in tumoral Hodgkin–Reed–Sternberg (HRS) cells of primary diagnostic samples of cHL. Formalin-Fixed Paraffin-Embedded (FFPE) lymph node samples from 88 patients with cHL were analyzed. Patients were treated with the standard first-line chemotherapy (CT) with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) followed by radiotherapy. The Kaplan–Meier method and the Cox proportional hazards model were used for carrying out the survival analysis. In order to investigate whether the influence of EBV was age-dependent, analyses were performed both for patients of all ages and for age-stratified subgroups. In bivariate analysis, the expression of EBV was associated with older age (p = 0.011), mixed cellularity subtype cHL (p < 0.001) and high risk International Prognostic Score (IPS) (p = 0.023). Overall survival (OS) and progression-free survival (PFS) were associated with the presence of bulky disease (p = 0.009) and advanced disease at diagnosis (p = 0.016). EBV-positive cases did not present a significantly lower OS and PFS in comparison with EBV-negative cases, for all ages and when stratifying for age. When adjusted for covariates, absence of bulky disease at diagnosis (HR: 0.102, 95% CI: 0.02–0.48, p = 0.004) and limited disease stages (I–II) (HR: 0.074, 95% CI: 0.01–0.47, p = 0.006) were associated with a significant better OS. For PFS, limited-disease stages also retained prognostic impact in the multivariate Cox regression (HR: 0.145, 95% CI: 0.04–0.57, p = 0.006). These results are of importance as the early identification of prognostic biomarkers in cHL is critical for guiding and personalizing therapeutic decisions. The prognostic role of EBV in cHL could be modulated by the type of CT protocol employed and interact with the rest of presenting features. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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14 pages, 2833 KiB  
Article
Development of Antibodies against HPV-6 and HPV-11 for the Study of Laryngeal Papilloma
by Taro Ikegami, Norimoto Kise, Hidetoshi Kinjyo, Shunsuke Kondo, Mikio Suzuki, Narutoshi Tsukahara, Akikazu Murakami, Asanori Kiyuna, Shinya Agena, Katsunori Tanaka, Narumi Hasegawa, Junko Kawakami, Akira Ganaha, Hiroyuki Maeda and Hitoshi Hirakawa
Viruses 2021, 13(10), 2024; https://0-doi-org.brum.beds.ac.uk/10.3390/v13102024 - 07 Oct 2021
Cited by 5 | Viewed by 2356
Abstract
Laryngeal papilloma (LP), which is associated with infection by human papillomavirus (HPV)-6 or -11, displays aggressive growth. The precise molecular mechanism underlying the tumorigenesis of LP has yet to be uncovered. Building on our earlier research into HPV-6, in this study, the viral [...] Read more.
Laryngeal papilloma (LP), which is associated with infection by human papillomavirus (HPV)-6 or -11, displays aggressive growth. The precise molecular mechanism underlying the tumorigenesis of LP has yet to be uncovered. Building on our earlier research into HPV-6, in this study, the viral gene expression of HPV-11 was investigated by quantitative PCR and DNA/RNA in situ hybridization. Additionally, newly developed antibodies against the E4 protein of HPV-6 and HPV-11 were evaluated by immunohistochemistry. The average viral load of HPV-11 in LP was 1.95 ± 0.66 × 105 copies/ng DNA, and 88% of HPV mRNA expression was found to be E4, E5a, and E5b mRNAs. According to RNA in situ hybridization, E4 and E5b mRNAs were expressed from the middle to upper part of the epithelium. E4 immunohistochemistry revealed a wide positive reaction in the upper cell layer in line with E4 mRNA expression. Other head and neck lesions with HPV-11 infection also showed a positive reaction in E4 immunohistochemistry. The distribution pattern of HPV DNA, viral mRNA, and E4 protein in LP with HPV-11 infection was quite similar to that of HPV-6. Therefore, it might be possible to apply these E4-specific antibodies in other functional studies as well as clinical applications, including targeted molecular therapies in patients with HPV-6 and HPV-11 infection. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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12 pages, 3795 KiB  
Article
Detection of Human Papillomavirus Integration in Brain Metastases from Oropharyngeal Tumors by Targeted Sequencing
by Brian McEllin, Brian C. Searle, Lisa DePledge, George Sun, Charles Cobbs and Mohsen Karimi
Viruses 2021, 13(8), 1536; https://0-doi-org.brum.beds.ac.uk/10.3390/v13081536 - 03 Aug 2021
Cited by 5 | Viewed by 2970
Abstract
Human papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) are known to have differential phenotypes, including the incidence and location of metastases. HPV positive (HPV+) HNSCC are more likely to metastasize to distant sites, such as the lung, brain, [...] Read more.
Human papillomavirus (HPV) positive and negative head and neck squamous cell carcinoma (HNSCC) are known to have differential phenotypes, including the incidence and location of metastases. HPV positive (HPV+) HNSCC are more likely to metastasize to distant sites, such as the lung, brain, and skin. Among these locations, metastasis to the brain is a rare event, and little is known about specific risk factors for this phenotype. In this report, we describe two patients who developed brain metastases from HNSCC. Both patient tumors had p16INK4a overexpression, suggesting these tumors were HPV+. This was confirmed after PCR, in situ hybridization, and mass spectrometry detected the presence of HPV type 16 (HPV16) DNA, RNA and protein. To further characterize the presence of HPV16, we used a target enrichment strategy on tumor DNA and RNA to isolate the viral sequences from the brain metastases. Analysis by targeted next generation sequencing revealed that both tumors had the HPV genome integrated into the host genome at known hotspots, 8q24.21 and 14q24.1. Applying a similar target enrichment strategy to a larger cohort of HPV+ HNSCC brain metastases could help to identify biomarkers that can predict metastasis and/or identify novel therapeutic options. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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10 pages, 247 KiB  
Article
Human Papillomavirus (HPV) DNA Detection Using Self-Sampling Devices in Women Undergoing Long Term Immunosuppressive Therapy
by Aleksandra Wielgos, Bronislawa Pietrzak, Mariusz Sikora, Gajane Martirosian, Barbara Suchonska, Jolanta Gozdowska, Urszula Oldakowska-Jedynak, Zoulikha Jabiry-Zieniewicz, Magdalena Durlik, Lidia Rudnicka and Miroslaw Wielgos
Viruses 2020, 12(9), 962; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090962 - 30 Aug 2020
Cited by 9 | Viewed by 2425
Abstract
Immunosuppression is a risk factor of persistent human papillomavirus (HPV) infections, which might lead to development of (pre)malignant lesions of the cervix and lower anogenital tract. Results of HPV DNA testing using cervicovaginal self-samples are comparable to those that are clinician-obtained and therefore [...] Read more.
Immunosuppression is a risk factor of persistent human papillomavirus (HPV) infections, which might lead to development of (pre)malignant lesions of the cervix and lower anogenital tract. Results of HPV DNA testing using cervicovaginal self-samples are comparable to those that are clinician-obtained and therefore might be used in cervical screening. The aim of this study was to assess the prevalence of high-risk HPV (hrHPV) infections, their risk factors and the genotypes distribution among women undergoing immunosuppressive therapy. Women undergoing immunosuppressive therapy for at least three months due to solid organ transplantation or autoimmune disorders were asked to self-collect samples for HPV testing using cervicovaginal brushes and complete questionnaires regarding cervical cancer risk factors. HPV DNA detection and genotyping were performed using Genotyping kit HPV GP version 2. hrHPV was detected in 26/90 (28.9%) specimens. Genotyping revealed a broad range of hrHPV, with type 16 being the most common genotype (11/26). The components of bivalent/quadrivalent or nonavalent vaccines cover all genotypes present in 4.4% and 17.8% women, respectively, and occur as a co-infection with other types in 12.2% and 23.3% of women, respectively. The only feature significantly associated with being hrHPV-positive was having at least two lifetime sexual partners. The high prevalence of hrHPV infections among immunosuppressed women emphasizes the need for regular cervical cancer screening with HPV DNA testing, which might be performed on self-collected specimen. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
18 pages, 2756 KiB  
Article
Upregulation of GLS1 Isoforms KGA and GAC Facilitates Mitochondrial Metabolism and Cell Proliferation in Epstein–Barr Virus Infected Cells
by Gayathri Krishna, Vinod Soman Pillai and Mohanan Valiya Veettil
Viruses 2020, 12(8), 811; https://0-doi-org.brum.beds.ac.uk/10.3390/v12080811 - 27 Jul 2020
Cited by 12 | Viewed by 3259
Abstract
Epstein–Barr virus or human herpesvirus 4 (EBV/HHV-4) is a ubiquitous human virus associated with a wide range of malignant neoplasms. The interaction between EBV latent proteins and host cellular molecules often leads to oncogenic transformation, promoting the development of EBV-associated cancers. The present [...] Read more.
Epstein–Barr virus or human herpesvirus 4 (EBV/HHV-4) is a ubiquitous human virus associated with a wide range of malignant neoplasms. The interaction between EBV latent proteins and host cellular molecules often leads to oncogenic transformation, promoting the development of EBV-associated cancers. The present study identifies a functional role of GLS1 isoforms KGA and GAC in regulating mitochondrial energy metabolism to promote EBV-infected cell proliferation. Our data demonstrate increased expression of GLS1 isoforms KGA and GAC with mitochondrial localization in latently EBV-infected cells and de novo EBV-infected PBMCs. c-Myc upregulates KGA and GAC protein levels, which in turn elevate the levels of intracellular glutamate. Further analysis demonstrated upregulated expression of mitochondrial GLUD1 and GLUD2, with a subsequent increase in alpha-ketoglutarate levels that may mark the activation of glutaminolysis. Cell proliferation and viability of latently EBV-infected cells were notably inhibited by KGA/GAC, as well as GLUD1 inhibitors. Taken together, our results suggest that c-Myc-dependent regulation of KGA and GAC enhances mitochondrial functions to support the rapid proliferation of the EBV-infected cells, and these metabolic processes could be therapeutically exploited by targeting KGA/GAC and GLUD1 to prevent EBV-associated cancers. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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13 pages, 1708 KiB  
Article
Whole Genomic Analysis and Comparison of Two Canine Papillomavirus Type 9 Strains in Malignant and Benign Skin Lesions
by Chia-Yu Chang, Nanako Yamashita-Kawanishi, Sonoka Tomizawa, I-Li Liu, Wei-Tao Chen, Yen-Chen Chang, Wei-Hsiang Huang, Pei-Shiue Tsai, Kinji Shirota, James K Chambers, Kazuyuki Uchida, Takeshi Haga and Hui-Wen Chang
Viruses 2020, 12(7), 736; https://0-doi-org.brum.beds.ac.uk/10.3390/v12070736 - 08 Jul 2020
Cited by 4 | Viewed by 2572
Abstract
Papillomaviruses (PVs) usually cause benign proliferative lesions in the stratified epithelium of various animal species. However, some high-risk types of PVs have been proven to lead to malignant transformations. In dogs, several canine papillomaviruses (CPVs) have been identified in malignant lesions and are [...] Read more.
Papillomaviruses (PVs) usually cause benign proliferative lesions in the stratified epithelium of various animal species. However, some high-risk types of PVs have been proven to lead to malignant transformations. In dogs, several canine papillomaviruses (CPVs) have been identified in malignant lesions and are suggested as one of the risk factors for the development of squamous cell carcinomas (SCCs). In the present study, the full genomes of two CPV9 strains from recurrent SCCs of Dog 1 and skin viral papilloma (viral plaque) of Dog 2 were sequenced. Alignment of the two CPV9 sequences with the genome of the reference CPV9 strain (accession no. JF800656.1) derived from a solitary pigmented plaque was performed. Compared with the reference strain, a 27 bp in-frame insertion in the E1 gene was identified in both CPV9 strains in this study. In comparison with the CPV9 strains derived from benign lesions, the CPV9 from the SCCs of Dog 1 exhibited a 328 bp deletion at the 3′ end of the E2 and spacer sequence, which encoded a truncated deduced E2 protein and a chimeric E8^E2 protein. However, there was no difference in the mRNA expression levels of viral oncoproteins of E6 and E7 between the two CPV9 cases, suggesting that the oncogenesis of CPV9 for malignant transformation might be different from that of human papillomaviruses. The roles of E2 and E8^E2 deleted CPV9 in the oncogenesis of benign and malignant lesions should be further investigated. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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19 pages, 6255 KiB  
Article
A Novel Retrovirus (Gunnison’s Prairie Dog Retrovirus) Associated With Thymic Lymphoma in Gunnison’s Prairie Dogs in Colorado, USA
by Molly D. Butler, Karen Griffin, Connie D. Brewster, Marylee L. Kapuscinski, Mark D. Stenglein, Daniel W. Tripp, Sandra L. Quackenbush and Karen A. Fox
Viruses 2020, 12(6), 606; https://0-doi-org.brum.beds.ac.uk/10.3390/v12060606 - 02 Jun 2020
Cited by 6 | Viewed by 3702
Abstract
As part of research and wildlife disease surveillance efforts, we performed necropsy examinations of 125 free-ranging (n = 114) and captive (n = 11) prairie dogs in Colorado from 2009 to 2017. From these cases, we identified three cases of thymic [...] Read more.
As part of research and wildlife disease surveillance efforts, we performed necropsy examinations of 125 free-ranging (n = 114) and captive (n = 11) prairie dogs in Colorado from 2009 to 2017. From these cases, we identified three cases of thymic lymphoma in free-ranging Gunnison’s prairie dogs (Cynomys gunnisoni), and we identified a novel retroviral sequence associated with these tumors. The viral sequence is 7700 nucleotides in length and exhibits a genetic organization that is consistent with the characteristics of a type D betaretrovirus. The proposed name of this virus is Gunnison’s prairie dog retrovirus (GPDRV). We screened all 125 prairie dogs for the presence of GPDRV using PCR with envelope-specific primers and DNA extracted from spleen samples. Samples were from Gunnison’s prairie dogs (n = 59), black-tailed prairie dogs (Cynomys ludovicianus) (n = 40), and white-tailed prairie dogs (Cynomys leucurus) (n = 26). We identified GPDRV in a total of 7/125 (5.6%) samples including all three of the prairie dogs with thymic lymphoma, as well as spleen from an additional four Gunnison’s prairie dogs with no tumors recognized at necropsy. None of the GPDRV-negative Gunnison’s prairie dogs had thymic lymphomas. We also identified a related, apparently endogenous retroviral sequence in all prairie dog samples. These results suggest that GPDRV infection may lead to development of thymic lymphoma in Gunnison’s prairie dogs. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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14 pages, 708 KiB  
Article
Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women
by Mariel A. Oyervides-Muñoz, Antonio A. Pérez-Maya, Celia N. Sánchez-Domínguez, Anais Berlanga-Garza, Mauro Antonio-Macedo, Lezmes D. Valdéz-Chapa, Ricardo M. Cerda-Flores, Victor Trevino, Hugo A. Barrera-Saldaña and María L. Garza-Rodríguez
Viruses 2020, 12(4), 380; https://0-doi-org.brum.beds.ac.uk/10.3390/v12040380 - 31 Mar 2020
Cited by 50 | Viewed by 4405
Abstract
Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and [...] Read more.
Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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Review

Jump to: Editorial, Research, Other

18 pages, 2057 KiB  
Review
Berberine in Human Oncogenic Herpesvirus Infections and Their Linked Cancers
by Miroslava Šudomová, Kateřina Berchová-Bímová, Stefania Marzocco, Alena Liskova, Peter Kubatka and Sherif T.S. Hassan
Viruses 2021, 13(6), 1014; https://0-doi-org.brum.beds.ac.uk/10.3390/v13061014 - 28 May 2021
Cited by 16 | Viewed by 4820
Abstract
Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug [...] Read more.
Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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30 pages, 2927 KiB  
Review
Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies
by Ethan L. Morgan and Andrew Macdonald
Viruses 2020, 12(9), 977; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090977 - 03 Sep 2020
Cited by 33 | Viewed by 5964
Abstract
Human papillomaviruses (HPVs) are small, DNA viruses that cause around 5% of all cancers in humans, including almost all cervical cancer cases and a significant proportion of anogenital and oral cancers. The HPV oncoproteins E5, E6 and E7 manipulate cellular signalling pathways to [...] Read more.
Human papillomaviruses (HPVs) are small, DNA viruses that cause around 5% of all cancers in humans, including almost all cervical cancer cases and a significant proportion of anogenital and oral cancers. The HPV oncoproteins E5, E6 and E7 manipulate cellular signalling pathways to evade the immune response and promote virus persistence. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has emerged as a key mediator in a wide range of important biological signalling pathways, including cell proliferation, cell survival and the immune response. While STAT1 and STAT2 primarily drive immune signalling initiated by interferons, STAT3 and STAT5 have widely been linked to the survival and proliferative potential of a number of cancers. As such, the inhibition of STAT3 and STAT5 may offer a therapeutic benefit in HPV-associated cancers. In this review, we will discuss how HPV manipulates JAK/STAT signalling to evade the immune system and promote cell proliferation, enabling viral persistence and driving cancer development. We also discuss approaches to inhibit the JAK/STAT pathway and how these could potentially be used in the treatment of HPV-associated disease. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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Other

12 pages, 1261 KiB  
Brief Report
Merkel Cell Polyomavirus in Merkel Cell Carcinoma: Integration Sites and Involvement of the KMT2D Tumor Suppressor Gene
by Reety Arora, Jae Eun Choi, Paul W. Harms and Pratik Chandrani
Viruses 2020, 12(9), 966; https://0-doi-org.brum.beds.ac.uk/10.3390/v12090966 - 31 Aug 2020
Cited by 7 | Viewed by 3166
Abstract
Merkel cell carcinoma (MCC) is an uncommon, lethal cancer of the skin caused by either Merkel cell polyomavirus (MCPyV) or UV-linked mutations. MCPyV is found integrated into MCC tumor genomes, accompanied by truncation mutations that render the MCPyV large T antigen replication incompetent. [...] Read more.
Merkel cell carcinoma (MCC) is an uncommon, lethal cancer of the skin caused by either Merkel cell polyomavirus (MCPyV) or UV-linked mutations. MCPyV is found integrated into MCC tumor genomes, accompanied by truncation mutations that render the MCPyV large T antigen replication incompetent. We used the open access HPV Detector/Cancer-virus Detector tool to determine MCPyV integration sites in whole-exome sequencing data from five MCC cases, thereby adding to the limited published MCPyV integration site junction data. We also systematically reviewed published data on integration for MCPyV in the human genome, presenting a collation of 123 MCC cases and their linked chromosomal sites. We confirmed that there were no highly recurrent specific sites of integration. We found that chromosome 5 was most frequently involved in MCPyV integration and that integration sites were significantly enriched for genes with binding sites for oncogenic transcription factors such as LEF1 and ZEB1, suggesting the possibility of increased open chromatin in these gene sets. Additionally, in one case we found, for the first time, integration involving the tumor suppressor gene KMT2D, adding to previous reports of rare MCPyV integration into host tumor suppressor genes in MCC. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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10 pages, 3985 KiB  
Case Report
Epstein–Barr Virus-Induced Post-Transplant Lymphoproliferative Disorder of the Central Nervous System Successfully Treated with Chemo-Immunotherapy
by Hiroaki Inoue, Shinya Rai, Hirokazu Tanaka, J. Luis Espinoza, Maiko Komori-Inoue, Hiroaki Kakutani, Shuji Minamoto, Takahiro Kumode, Shoko Nakayama, Yasuhiro Taniguchi, Yasuyoshi Morita, Takeshi Okuda, Yoichi Tatsumi, Takashi Ashida and Itaru Matsumura
Viruses 2020, 12(4), 416; https://0-doi-org.brum.beds.ac.uk/10.3390/v12040416 - 08 Apr 2020
Cited by 4 | Viewed by 2728
Abstract
Aplastic anemia is a rare blood disease characterized by the destruction of the hematopoietic stem cells (HSC) in the bone marrow that, in the majority of cases, is caused by an autoimmune reaction. Patients with aplastic anemia are treated with immunosuppressive drugs and [...] Read more.
Aplastic anemia is a rare blood disease characterized by the destruction of the hematopoietic stem cells (HSC) in the bone marrow that, in the majority of cases, is caused by an autoimmune reaction. Patients with aplastic anemia are treated with immunosuppressive drugs and some of them, especially younger individuals with a donor available, can be successfully treated with hematopoietic stem cell transplantation (HSCT). We report here a rare case of post-transplant lymphoproliferative disorder (PTLD) associated with Epstein–Barr virus (EBV) reactivation in a 30-year-old female patient who underwent allogeneic HSCT for severe aplastic anemia. The PTLD, which was diagnosed 230 days after transplantation, was localized exclusively in the central nervous system (specifically in the choroid plexus) and manifested with obvious signs of intracranial hypertension. After receiving three cycles of high dose methotrexate (HD-MTX) combined with rituximab, the patient achieved a complete clinical recovery with normalization of blood cell counts, no evidence of EBV reactivation, and no associated neurotoxicity. Full article
(This article belongs to the Special Issue Recent Progress in Tumor Virology Research)
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