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Identification of an Overprinting Gene in Merkel Cell Polyomavirus Provides Evolutionary Insight Into the Birth of Viral Genes
Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes Joseph J. Cartera,b,1,2, Matthew D. Daughertyc,1, Xiaojie Qia, Anjali Bheda-Malgea,3, Gregory C. Wipfa, Kristin Robinsona, Ann Romana, Harmit S. Malikc,d, and Denise A. Gallowaya,b,2 Divisions of aHuman Biology, bPublic Health Sciences, and cBasic Sciences and dHoward Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 Edited by Peter M. Howley, Harvard Medical School, Boston, MA, and approved June 17, 2013 (received for review February 24, 2013) Many viruses use overprinting (alternate reading frame utiliza- mammals and birds (7, 8). Polyomaviruses leverage alternative tion) as a means to increase protein diversity in genomes severely splicing of the early region (ER) of the genome to generate pro- constrained by size. However, the evolutionary steps that facili- tein diversity, including the large and small T antigens (LT and ST, tate the de novo generation of a novel protein within an ancestral respectively) and the middle T antigen (MT) of murine poly- ORF have remained poorly characterized. Here, we describe the omavirus (MPyV), which is generated by a novel splicing event and identification of an overprinting gene, expressed from an Alter- overprinting of the second exon of LT. Some polyomaviruses can nate frame of the Large T Open reading frame (ALTO) in the early drive tumorigenicity, and gene products from the ER, especially region of Merkel cell polyomavirus (MCPyV), the causative agent SV40 LT and MPyV MT, have been extraordinarily useful models of most Merkel cell carcinomas. -
Merkel Cell Polyomavirus DNA in Immunocompetent and Immunocompromised Patients with Respiratory Disease
Journal of Medical Virology 83:2220–2224 (2011) Merkel Cell Polyomavirus DNA in Immunocompetent and Immunocompromised Patients With Respiratory Disease Bahman Abedi Kiasari,1,3* Pamela J. Vallely,1 and Paul E. Klapper1,2 1Department of Virology, Genomic Epidemiology Research Group, School of Translational Medicine, University of Manchester, Manchester, United Kingdom 2Clinical Virology, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Oxford Road, Manchester, United Kingdom 3Human Viral Vaccine Department, Razi Vaccine & Serum Research Institute, Hesarak, Karaj, Iran Merkel cell polyomavirus (MCPyV) was identi- INTRODUCTION fied originally in association with a rare but aggressive skin cancer, Merkel cell carcinoma. In the past few years, a number of new human poly- The virus has since been found in the respirato- omaviruses, KI, WU, human polyomavirus 6 (HPyV6), ry tract of some patients with respiratory human polyomavirus 7 (HPyV7), trichodysplasia spi- disease. However, the role of MCPyV in the nulosa virus (TSV), human polyomavirus 9 (HPyV9), causation of respiratory disease has not been and Merkel cell polyomavirus (MCPyV) have been established. To determine the prevalence of discovered [Allander et al., 2007; Gaynor et al., 2007; MCPyV in 305 respiratory samples from Feng et al., 2008; Schowalter et al., 2010; van der immunocompetent and immunocompromised Meijden et al., 2010; Scuda et al., 2011]. MCPyV was patients and evaluate their contribution to re- discovered by digital transcriptome subtraction from a spiratory diseases, specimens were screened human skin cancer, Merkel cell carcinoma [Feng for MCPyV using single, multiplex, or real-time et al., 2008]. The finding of MCPyV in human Merkel PCR; co-infection with other viruses was exam- cell carcinoma suggests a role for this virus in the ined. -
An Overview on Human Polyomaviruses Developing Cancer
The Journal of Medical Research 2020; 6(4): 125-127 Review Article An overview on human polyomaviruses developing cancer in JMR 2020; 6(4): 125-127 humans July- August ISSN: 2395-7565 Mohammad Salim1, Mohammad Shahid Masroor2, Shagufta parween3, I.P. Prajapati1 © 2020, All rights reserved 1 Sanjay Gandhi Smriti Govt. Autonomous P.G. College, Sidhi, (affiliated to APS University, Rewa), Madhya Pradesh- www.medicinearticle.com 486661, India Received: 22-06-2020 2 People’s College of Dental Sciences & Research Center, People's University, Bhopal, Madhya Pradesh- 462037, Accepted: 14-07-2020 India 3 All India Institute of Medical sciences (AIIMS), Bhopal, Madhya Pradesh-462020, India Abstract The family Polyomaviridae included about a dozen of human polyomaviruses (HPyVs), of which MCPyV, SV-40, JCV and BKV viruses have been reported to cause cancer in human. Merkel cell carcinoma is a very aggressive type of skin cancer caused by the MCPyV5. Similarly, while SV-40 and JCV viruses developed brain tumor cancer, the BK virus has been linked to renal transplantations and nephropathy producing urinary bladder tumor and prostate cancer in human. In this paper we have tried to summarize the recent information gained in the field of human polyomaviruses causing cancer in human. Keywords: Human polyomaviruses, Cancer, Virus. INTRODUCTION Viruses are among the few causes of cancer contributing to a variety of malignancies. In 1966, when Peyton Rous was awarded a Nobel prize in physiology and medicine for his discovery of Rous chicken sarcoma virus as a cause of cancer, a renewed interest came in the field of microbial origin of cancer. -
Viruses in Transplantation - Not Always Enemies
Viruses in transplantation - not always enemies Virome and transplantation ECCMID 2018 - Madrid Prof. Laurent Kaiser Head Division of Infectious Diseases Laboratory of Virology Geneva Center for Emerging Viral Diseases University Hospital of Geneva ESCMID eLibrary © by author Conflict of interest None ESCMID eLibrary © by author The human virome: definition? Repertoire of viruses found on the surface of/inside any body fluid/tissue • Eukaryotic DNA and RNA viruses • Prokaryotic DNA and RNA viruses (phages) 25 • The “main” viral community (up to 10 bacteriophages in humans) Haynes M. 2011, Metagenomic of the human body • Endogenous viral elements integrated into host chromosomes (8% of the human genome) • NGS is shaping the definition Rascovan N et al. Annu Rev Microbiol 2016;70:125-41 Popgeorgiev N et al. Intervirology 2013;56:395-412 Norman JM et al. Cell 2015;160:447-60 ESCMID eLibraryFoxman EF et al. Nat Rev Microbiol 2011;9:254-64 © by author Viruses routinely known to cause diseases (non exhaustive) Upper resp./oropharyngeal HSV 1 Influenza CNS Mumps virus Rhinovirus JC virus RSV Eye Herpes viruses Parainfluenza HSV Measles Coronavirus Adenovirus LCM virus Cytomegalovirus Flaviviruses Rabies HHV6 Poliovirus Heart Lower respiratory HTLV-1 Coxsackie B virus Rhinoviruses Parainfluenza virus HIV Coronaviruses Respiratory syncytial virus Parainfluenza virus Adenovirus Respiratory syncytial virus Coronaviruses Gastro-intestinal Influenza virus type A and B Human Bocavirus 1 Adenovirus Hepatitis virus type A, B, C, D, E Those that cause -
Identification of the Neutralizing Epitopes of Merkel Cell Polyomavirus Major Capsid Protein Within the BC and EF Surface Loops Maxime J J Fleury, Jérôme T.J
Identification of the neutralizing epitopes of Merkel cell polyomavirus major capsid protein within the BC and EF surface loops Maxime J J Fleury, Jérôme T.J. Nicol, Mahtab Samimi-Gharaei, Françoise Arnold, Raphael Cazal, Raphaelle Ballaire, Olivier Mercey, Hélène Gonneville, Nicolas Combelas, Jean-François Vautherot, et al. To cite this version: Maxime J J Fleury, Jérôme T.J. Nicol, Mahtab Samimi-Gharaei, Françoise Arnold, Raphael Cazal, et al.. Identification of the neutralizing epitopes of Merkel cell polyomavirus major capsid protein within the BC and EF surface loops. PLoS ONE, Public Library of Science, 2015, 10 (3), pp.1-13. 10.1371/journal.pone.0121751. hal-01190152 HAL Id: hal-01190152 https://hal.archives-ouvertes.fr/hal-01190152 Submitted on 1 Sep 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License RESEARCH ARTICLE Identification of the Neutralizing Epitopes of Merkel Cell Polyomavirus Major Capsid Protein within the BC and EF Surface Loops Maxime J. J. Fleury1, -
Detection and Quantification of Classic and Emerging Viruses by Skimmed
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by CONICET Digital water research xxx (2013) 1e14 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/watres Detection and quantification of classic and emerging viruses by skimmed-milk flocculation and PCR in river water from two geographical areas Byron Calgua a, Tulio Fumian b, Marta Rusin˜ola, Jesus Rodriguez-Manzano a, Viviana A. Mbayed c, Silvia Bofill-Mas a, Marize Miagostovich b, Rosina Girones a,* a Department of Microbiology, Faculty of Biology, University of Barcelona, Av. Diagonal 643, Barcelona 08028, Spain b Laboratory of Comparative and Environmental Virology, Oswaldo Cruz Institute, Avenida Brasil 4365, Rio de Janeiro, Brazil c Laboratory of Virology, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Junı´n 956, Buenos Aires, Argentina article info abstract Article history: Molecular techniques and virus concentration methods have shown that previously un- Received 24 September 2012 known viruses are shed by humans and animals, and may be transmitted by sewage- Received in revised form contaminated water. In the present study, 10-L river-water samples from urban areas in 16 February 2013 Barcelona, Spain and Rio Janeiro, Brazil, have been analyzed to evaluate the viral Accepted 21 February 2013 dissemination of human viruses, validating also a low-cost concentration method for virus Available online xxx quantification in fresh water. Three viral groups were analyzed: (i) recently reported vi- ruses, klassevirus (KV), asfarvirus-like virus (ASFLV), and the polyomaviruses Merkel cell Keywords: (MCPyV), KI (KIPyV) and WU (WUPyV); (ii) the gastroenteritis agents noroviruses (NoV) and Emerging virus rotaviruses (RV); and (iii) the human fecal viral indicators in water, human adenoviruses Polyomavirus (HAdV) and JC polyomaviruses (JCPyV). -
Antibodies Response to Polyomaviruses Primary Infection: High Seroprevalence of Merkel Cell
Antibodies response to Polyomaviruses primary infection: high seroprevalence of Merkel Cell Polyomavirus and lymphoid tissues involvement. Carolina Cason1, Lorenzo Monasta2, Nunzia Zanotta2, Giuseppina Campisciano2, Iva Maestri3, Massimo Tommasino4, Michael Pawlita5, Sonia Villani6, Manola Comar1,2, Serena Delbue6,*. Authors affiliations: 1 Department of Medical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy. 2Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell' Istria 65/1, 34137 Trieste, Italy. 3Department of Experimental and Diagnostic Medicine, Pathology Unit of Pathologic Anatomy, Histology and Cytology University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy. 4Infections and Cancer Biology Group, International Agency for Research on Cancer, Cours Albert Thomas 150, 69372 Lyon, France. 5German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. 6Department of Biomedical, Surgical & Dental Sciences, University of Milano, Via Pascal 36, 20100 Milano, Italy. * Corresponding author: [email protected], +390250315070 1 ABSTRACT Human polyomaviruses (HPyVs) asymptomatically infect the human population establishing latency in the host and their seroprevalence can reach 90% in healthy adults. Few studies have focused on the pediatric population and there are no reports regarding the seroprevalence of all the newly isolated HPyVs among Italian children. Therefore, we investigated the frequency of serum antibodies against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of a multiplex antibody detection system. Additionally, secondary lymphoid tissues were collected to analyze the presence of HPyVs DNA sequences using a specific Real Time PCRs or PCRs. Almost 100% of subjects were seropositive for at least one PyV. Seropositivity ranged from 3% for antibodies against Simian virus 40 (SV40) in children from 0 to 3 years, to 91% for antibodies against WU polyomavirus (WUPyV) and HPyV10 in children from 8 to 17 years. -
Cancer Patients Have a Higher Risk Regarding COVID-19–And Vice Versa?
pharmaceuticals Opinion Cancer Patients Have a Higher Risk Regarding COVID-19–and Vice Versa? Franz Geisslinger, Angelika M. Vollmar and Karin Bartel * Pharmaceutical Biology, Department Pharmacy, Ludwig-Maximilians-University of Munich, 81377 Munich, Germany; [email protected] (F.G.); [email protected] (A.M.V.) * Correspondence: [email protected] Received: 29 May 2020; Accepted: 3 July 2020; Published: 6 July 2020 Abstract: The world is currently suffering from a pandemic which has claimed the lives of over 230,000 people to date. The responsible virus is called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and causes the coronavirus disease 2019 (COVID-19), which is mainly characterized by fever, cough and shortness of breath. In severe cases, the disease can lead to respiratory distress syndrome and septic shock, which are mostly fatal for the patient. The severity of disease progression was hypothesized to be related to an overshooting immune response and was correlated with age and comorbidities, including cancer. A lot of research has lately been focused on the pathogenesis and acute consequences of COVID-19. However, the possibility of long-term consequences caused by viral infections which has been shown for other viruses are not to be neglected. In this regard, this opinion discusses the interplay of SARS-CoV-2 infection and cancer with special focus on the inflammatory immune response and tissue damage caused by infection. We summarize the available literature on COVID-19 suggesting an increased risk for severe disease progression in cancer patients, and we discuss the possibility that SARS-CoV-2 could contribute to cancer development. -
The Mirna World of Polyomaviruses Ole Lagatie1*, Luc Tritsmans2 and Lieven J Stuyver1
Lagatie et al. Virology Journal 2013, 10:268 http://www.virologyj.com/content/10/1/268 REVIEW Open Access The miRNA world of polyomaviruses Ole Lagatie1*, Luc Tritsmans2 and Lieven J Stuyver1 Abstract Polyomaviruses are a family of non-enveloped DNA viruses infecting several species, including humans, primates, birds, rodents, bats, horse, cattle, raccoon and sea lion. They typically cause asymptomatic infection and establish latency but can be reactivated under certain conditions causing severe diseases. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in several cellular processes by binding to and inhibiting the translation of specific mRNA transcripts. In this review, we summarize the current knowledge of microRNAs involved in polyomavirus infection. We review in detail the different viral miRNAs that have been discovered and the role they play in controlling both host and viral protein expression. We also give an overview of the current understanding on how host miRNAs may function in controlling polyomavirus replication, immune evasion and pathogenesis. Keywords: Polyomaviruses, microRNAs, Virus-host interaction, Immune evasion Review for BKPyV, Merkel cell carcinoma (MCC) for Merkel General overview of polyomaviruses Cell Virus (MCPyV) and trichodysplasia spinulosa for Polyomaviruses comprise a family of DNA tumor vi- Trichodysplasia spinulosa-associated Polyomavirus (TSPyV) ruses. They are non-enveloped and have a circular, [4,10,11,14-20]. One of the most striking observations is the double stranded DNA genome of around 5,100 bp [1]. fact that asymptomatic infection occurs during childhood The virion consists of 72 pentamers of the capsid pro- which is followed ordinarily by life-long asymptomatic tein VP1 with a single copy of VP2 and VP3 associated persistence [21]. -
Human Merkel Cell Polyomavirus Small T Antigen Is an Oncoprotein
Research article Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator Masahiro Shuda, Hyun Jin Kwun, Huichen Feng, Yuan Chang, and Patrick S. Moore Cancer Virology Program, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Merkel cell polyomavirus (MCV) is the recently discovered cause of most Merkel cell carcinomas (MCCs), an aggressive form of nonmelanoma skin cancer. Although MCV is known to integrate into the tumor cell genome and to undergo mutation, the molecular mechanisms used by this virus to cause cancer are unknown. Here, we show that MCV small T (sT) antigen is expressed in most MCC tumors, where it is required for tumor cell growth. Unlike the closely related SV40 sT, MCV sT transformed rodent fibroblasts to anchorage- and contact-independent growth and promoted serum-free proliferation of human cells. These effects did not involve protein phosphatase 2A (PP2A) inhibition. MCV sT was found to act downstream in the mam- malian target of rapamycin (mTOR) signaling pathway to preserve eukaryotic translation initiation factor 4E–binding protein 1 (4E-BP1) hyperphosphorylation, resulting in dysregulated cap-dependent translation. MCV sT–associated 4E-BP1 serine 65 hyperphosphorylation was resistant to mTOR complex (mTORC1) and mTORC2 inhibitors. Steady-state phosphorylation of other downstream Akt-mTOR targets, including S6K and 4E-BP2, was also increased by MCV sT. Expression of a constitutively active 4E-BP1 that could not be phosphorylated antagonized the cell transformation activity of MCV sT. Taken together, these experiments showed that 4E-BP1 inhibition is required for MCV transformation. Thus, MCV sT is an oncoprotein, and its effects on dysregulated cap-dependent translation have clinical implications for the prevention, diagnosis, and treatment of MCV-related cancers. -
Detection of Quebec Polyomavirus DNA in Samples from Different Patient Groups
microorganisms Communication Detection of Quebec Polyomavirus DNA in Samples from Different Patient Groups Carla Prezioso 1,2, Marijke Van Ghelue 3,4, Valeria Pietropaolo 1,* and Ugo Moens 5,* 1 Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, 00185 Rome, Italy; [email protected] 2 IRCSS San Raffaele Pisana, Microbiology of Chronic Neuro-degenerative Pathologies, 00163 Rome, Italy 3 Department of Medical Genetics, Division of Child and Adolescent Health, University Hospital of North Norway, 9038 Tromsø, Norway; [email protected] 4 Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, 9037 Tromsø, Norway 5 Department of Medical Biology, Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, 9037 Tromsø, Norway * Correspondence: [email protected] (V.P.); [email protected] (U.M.) Abstract: Polyomaviruses infect many species, including humans. So far, 15 polyomaviruses have been described in humans, but it remains to be established whether all of these are genuine human polyomaviruses. The most recent polyomavirus to be detected in a person is Quebec polyomavirus (QPyV), which was identified in a metagenomic analysis of a stool sample from an 85-year-old hospitalized man. We used PCR to investigate the presence of QPyV DNA in urine samples from systemic lupus erythematosus (SLE) patients (67 patients; 135 samples), multiple sclerosis patients (n = 35), HIV-positive patients (n = 66) and pregnant women (n = 65). Moreover, cerebrospinal fluid from patients with suspected neurological diseases (n = 63), nasopharyngeal aspirates from patients Citation: Prezioso, C.; Van Ghelue, (n = 80) with respiratory symptoms and plasma samples from HIV-positive patients (n = 65) were M.; Pietropaolo, V.; Moens, U. -
Advances in Human Polyomaviruses Field
rren : Cu t R y es g e lo a o r r c i h V Virology: Current Research Ciotti, Virol Curr Res 2017, 1:1 Editorial Open Access Advances in Human Polyomaviruses Field Marco Ciotti* Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133 Rome, Italy *Corresponding author: Ciotti M, Laboratory of Molecular Virology, Polyclinic Tor Vergata Foundation, Viale Oxford 81, 00133 Rome, Italy, Tel: +390620902087; E-mail: [email protected] Received date: February 27, 2017; Accepted date: March 02, 2017; Published date: March 02, 2017 Copyright: © 2017 Ciotti M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Editorial References Polyomaviruses are small non-enveloped DNA viruses with a 1. Gardner SD, Field AM, Coleman DV, Hulme B (1971) New human circular double stranded genome of about 5 Kb in length. The genome papovavirus (B.K.) isolated from urine after renal transplantation. Lancet is contained in a capsid with icosahedral structure of about 45 nm in 1: 1253-1257. diameter. 2. Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH (1971) Cultivation of papova-like virus from human brain with progressive Up to 2007, two human polyomaviruses BK (BKPyV) and JC multifocal leucoencephalopathy. Lancet 1: 1257-1260. (JCPyV) were known and named after the initials of the patients where 3. Allander T, Andreasson K, Gupta S, Bjerkner A, Bogdanovic G, et al. they were first isolated. BKV was isolated from the urine of a kidney (2007) Identification of a Third Human Polyomavirus.