DNA from Human Polyomaviruses, Mwpyv, Hpyv6, Hpyv7, Hpyv9

Total Page:16

File Type:pdf, Size:1020Kb

DNA from Human Polyomaviruses, Mwpyv, Hpyv6, Hpyv7, Hpyv9 ANTICANCER RESEARCH 38 : 4111-4114 (2018) doi:10.21873/anticanres.12701 DNA from Human Polyomaviruses, MWPyV, HPyV6, HPyV7, HPyV9 and HPyV12 in Cutaneous T-cell Lymphomas MASSIMILIANO BERGALLO 1, VALENTINA DAPRÀ 1, PAOLO FAVA 2, RENATA PONTI 2, CRISTINA CALVI 1, PAOLA MONTANARI 1, MAURO NOVELLI 2, PIETRO QUAGLINO 2, ILARIA GALLIANO 1 and MARIA TERESA FIERRO 2 1Department of Pediatrics, Infectious Diseases Unit, Regina Margherita Children’s Hospital, University of Turin, Turin, Italy; 2Department of Medical Sciences, Dermatology Section, University of Turin, Turin, Italy Abstract. Background/Aim: The etiopathogenesis of characterized by longstanding, scaly patch lesions mycosis fungoides and Sézary syndrome remains obscure. preferentially involving the buttocks and body areas Different viruses have been proposed to have a role in the infrequently exposed to sunlight. Disease progress is slow etiopathogenesis of cutaneous T-cell lymphomas (CTCL). In over years, from patches to plaques and eventually tumors or the present study, the presence of five recently discovered erythroderma. Lymph node and visceral involvement, as well human polyomaviruses 6 (HPyV6), human polyomaviruses 7 as large cell transformation, usually occur in the late stages of (HPyV7), human polyomaviruses 9 (HPyV9), human the disease (1). Sézary syndrome (SS) is an erythrodermic polyomaviruses 12 (HPyV12), and Malawi polyomavirus cutaneous T-cell lymphoma with leukemic involvement, with (MWPyV), have been analyzed in 55 CTCL in order to an aggressive clinical behavior and poor prognosis (2, 3). confirm the skin tropism and the possible pathological The etiopathogenesis of MF and SS remains obscure. association of these new polyomaviruses. Materials and Persistent antigen stimulation could lead to a continuous Methods: Human polyomaviruses DNA were amplified from proliferation of T-cells and chronic inflammation and, skin lesions were recovered from a total of 55 patients (32 ultimately, to the development of a malignant T-cell clone males and 23 females, average age 63±15 years) affected by (4). Another hypothesis suggests that specific viral agents CTCL. Results: When assayed for the presence of 5 different may serve as triggering factors (5). Different viruses have HPyVs, (HPyV6, HPyV7, HPyV9, MWPyV, and HPyV12) been suggested to have a role in the etiopathogenesis of HPyV9, HPyV10 and HPyV12 DNA sequences were not CTCL, mainly the human T-cell leukemia virus and the found in any skin specimens. HPyV6 and 7 DNA was Epstein-Barr virus (6, 7). Contradictory results have arisen detected in 1/55 (1.8%) of skin specimens. Conclusion: The from studies investigating the role of the Epstein-Barr virus low-level presence of HPyV6 and HPyV7 DNA, and lack of in CTCL (8). Our group demonstrated in previous reports detection of polyomaviruses HPyV9, MWPyV and HPyV12 that the Epstein-Barr virus, parvovirus variants (B19, in our series do not support a significant role of these HPyVs LaL1/K71, V9), human herpesvirus 7 (HHV-7), and human subtypes in the etiopathogenesis of skin cancers. polyomaviruses (HPyVs) HPyV6, HPyV7 and TSPyV were not involved in CTCL pathogenesis (9-11). Cutaneous T-cell lymphoma (CTCL) is a group of More specifically, the first HPyVs, polyomavirus BK malignancies derived from skin-homing T cells. Mycosis (BKPyV) and polyomavirus JC (JCPyV), were discovered in fungoides (MF) and Sézary syndrome (SS) are the most 1971, but it was not until 2007, that two more HPyVs, common CTCL variants. Mycosis fungoides (MF) is polyomavirus KI (KIPyV) and polyomavirus (WUPyV), were discovered in nasal aspirates (12, 13) followed by Merkel Cell polyomavirus (MCPyV), isolated from Merkel Cell Carcinomas (MCC) in 2008 (14). Since then, seven new HPyVs have been Correspondence to: Massimiliano Bergallo, Department of Public characterized from samples derived from the skin (Human Health and Pediatric Sciences, University of Turin, Medical School, polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7) and 10136 Turin, Italy. Tel: +39 0113135414, Fax: +39 0113135416, e-mail: [email protected] Trichodysplasia Spinulosa polyomavirus (TSPyV)) (15-17), blood (human polyomavirus 9 (HPyV9)) (18, 19), feces Key Words: Human polyomavirus, cutaneous T-cell lymphomas, (Malawi polyomavirus (MWPyV) and STL polyomavirus mycosis fungoides, Sézary syndrome. (STLPyV)) (20, 21), and from the gastrointestinal tract (human 4111 ANTICANCER RESEARCH 38 : 4111-4114 (2018) Table I. Primer and probe sequences used for the amplification of human polyomaviruses (HPyVs). Target Orientation Sequences Location HPyV6 Sense 5’-AAGTGGGAAGTGCTGGATATATAAGAG-3’ KX379631.1 1624-1650 Antisense 5’-TCCACAGGCCCAAAAGTACAT-3’ 1719-1699 Probe FAM-CCCCTGCTGGTGTAGAAGGTTCCCA-TAMRA 1673-1697 HPyV7 Sense 5’-TGCTGCAGTGCAAGAAGTTACA-3’ KX771235.1 2241-2262 Antisense 5’-CCAAGGCCTCCCTCAACA -3’ 2315-2298 Probe FAM-CAAATGCAGCCTGCTACTATCCCTCCAA-TAMRA 2269-2296 HPyV9 Sense 5’-CTAGGGAACAATTTGAATATCAGGAA-3’ HQ696595.1 1227-1252 Antisense 5’-ATAGTGTCCAGATCTAGGCTCTGAAC-3’ 1306-1281 Probe FAM-AAGTTAGGCTGAGGCGGGAGATAGGG-TAMRA 1254-1279 MWPyV Sense 5’-CATTGATGGACAGCCAATGG-3’ JX262162.1 2387-2406 Antisense 5’-TCCTGGAAGAGGTTCTGTTCCTT-3’ 2468-2446 Probe FAM-TGGGACTGATAATCAAGTACAGGATGTAACTGTGT-TAMRA 2408-2442 HPyV12 Sense 5’-GTGGGAAGCTGTCAGTGTGA-3’ JX308829.1 1731-1750 Antisense 5’-CCACCTACTGCAAACATGTG-3’ 1868-1849 Probe FAM-ACTACAGGATGGCCTACCCCATTGTCAGTC-TAMRA 1835-1806 polyomavirus 12 (HPyV12)) (22). Like most HPyVs, they are consent, and the study was approved by the Ethics Committee of also present in a large part of the general population, and their the ‘A.O.U. Città della Salute e della Scienza di Torino’. Cryostatic seroprevalence ranges from 20% to >90%, with HPyV9 being sections OCT-embedded (Tissue-TeK O.C.T. Compound, Sakura Eu, The Netherlands) from skin lesions were recovered from a total of the less common among them (23-25). Moreover, some HPyVs, 55 patients (32 males and 23 females, average age 63±15 years) i.e. , BKPyV, JCPyV, MCPyV and TSPyV, have clearly been affected by CTCL. All patients had been referred to the Section of associated with specific diseases and cancer (26-27). In Dermatology, at the Department of Medical Sciences of the immunocompromised individuals, reactivation of BKPyV is University of Turin. Diagnosis was histologically confirmed; 43/55 associated with haemorrhagic cystisis, BKV nephropathy, and patients had MF, 8/55 had SS; and 4/55 had primary cutaneous T- ureteral stenosis, while JCPyV is associated with progressive cell lymphoma (CTCL) non-MF/SS. multifocal leukoencephalopathy and TSPyV associated with DNA extraction. OCT-sections were incubated overnight at room Trichodysplasia spinulosa, a rare skin disease (27). As noted temperature with 500 μl of lysis buffer (100 mM NaCl, 10 mM Tris above, MCPyV is a frequent cause of the skin malignancy HCl pH8, 1 mM EDTA pH8, 1% SDS, 2% Triton X-100). The tubes Merkel cell carcinoma (MCC), mainly in immunosuppressed or were incubated at +100˚C for 10 min. Equal volumes of phenol- older individuals (14). However, despite that only MCPyV has chloroform were added to the sample and the tubes were centrifuged been associated with cancer, most other HPyVs express proteins at 12,000 rpm for 10 min. Upper aqueous phase was transferred into that may potentially contribute to cancer development; all, fresh tubes, followed by adding 1 volume of ice cold ethanol, and incubated at –20˚C for 1h and centrifuged at 12,000 rpm for 10 min except HPyV12, have putative binding sites for the at +4˚C. The DNA pellets were separated from supernatants and retinoblastoma protein and many also for p53 (16,17, 19, 22). washed twice with 70% ethanol; then, re-centrifuged at 12,000 rpm Herein, the presence of five recently discovered HPyVs, for 10 min and left to air-dry at room temperature. The pellets were HPyV6, HPyV7, HPyV9, HPyV12 and MWPyV, was dissolved in 20 μl of distilled water. The DNA samples were stored analyzed in 55 CTCL in order to confirm the possible skin at −20˚C until assayed. tropism and the possible pathological association of these Real-Time PCR. new polyomaviruses with the development of CTCL. Primers and probes sets for HPyV detection are shown in Table I. Sets of primers and a probe targeting Small tumor antigen (STa), a part of early expressed genome of Materials and Methods polyomaviruses, were designed using Primer Express Software Version 3.0 (Thermo Fisher, Paisley UK). The primers/probes Patients and samples. The present study was performed in concentration was compliance with the principles of good clinical practice and 900 nM/250 nM for each target. Real-Time PCR assays were according to the principles of the Declaration of Helsinki. All the performed using the GoTaQ qPCR MasterMix (Promega, Milano patients were included after providing their written informed IT), on the 7500 Real-Time PCR System (Life Technologies Ltd) 4112 Bergallo et al : Human Polyomaviruses in CTCL HPyV6, HPyV7, HPyV9, and MWPyV are all in general common in the population and sequence data suggests they all are potentially oncogenic, by binding to Rb and p53. Thus, the possibility that one or more of these viruses are causative for a subset of tumors is a plausible hypothesis (29). The tropism of these viruses is not well understood. HPyV6 and HPyV7 are, similarly to MCPyV, common on skin (30). HPyV9 is mainly, although rarely, found in the blood, but has also been isolated from skin (17) and in a serum sample from a kidney transplant patient (18). MWPyV, isolated
Recommended publications
  • 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,
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Polyomavirus
    GLOBAL WATER PATHOGEN PROJECT PART THREE. SPECIFIC EXCRETED PATHOGENS: ENVIRONMENTAL AND EPIDEMIOLOGY ASPECTS POLYOMAVIRUS Silvia Bofill-Mas University of Barcelona Barcelona, Spain Copyright: This publication is available in Open Access under the Attribution-ShareAlike 3.0 IGO (CC-BY-SA 3.0 IGO) license (http://creativecommons.org/licenses/by-sa/3.0/igo). By using the content of this publication, the users accept to be bound by the terms of use of the UNESCO Open Access Repository (http://www.unesco.org/openaccess/terms-use-ccbysa-en). Disclaimer: The designations employed and the presentation of material throughout this publication do not imply the expression of any opinion whatsoever on the part of UNESCO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. The ideas and opinions expressed in this publication are those of the authors; they are not necessarily those of UNESCO and do not commit the Organization. Citation: Bofill-Mas, S. (2016). Polyomavirus. In: J.B. Rose and B. Jiménez-Cisneros, (eds) Water and Sanitation for the 21st Century: Health and Microbiological Aspects of Excreta and Wastewater Management (Global Water Pathogen Project). (J.S Meschke, and R. Girones (eds), Part 3: Specific Excreted Pathogens: Environmental and Epidemiology Aspects - Section 1: Viruses), Michigan State University, E. Lansing, MI, UNESCO. https://doi.org/10.14321/waterpathogens.16 Acknowledgements: K.R.L. Young, Project Design editor; Website Design: Agroknow (http://www.agroknow.com) Last published: August 12, 2016 Polyomavirus Summary HPyVs are not “classic” waterborne pathogens. Their presence in water environments is a relatively recent discovery and they are thus considered as emerging or Human Polyomaviruses (HPyVs) are small, non- potentially emerging waterborne pathogens.
    [Show full text]
  • An Antibody Response to Human Polyomavirus 15-Mer Peptides Is Highly Abundant in Healthy Human Subjects
    Stuyver et al. Virology Journal 2013, 10:192 http://www.virologyj.com/content/10/1/192 RESEARCH Open Access An antibody response to human polyomavirus 15-mer peptides is highly abundant in healthy human subjects Lieven J Stuyver1*, Tobias Verbeke2, Tom Van Loy1, Ellen Van Gulck3 and Luc Tritsmans4 Abstract Background: Human polyomaviruses (HPyV) infections cause mostly unapparent or mild primary infections, followed by lifelong nonpathogenic persistence. HPyV, and specifically JCPyV, are known to co-diverge with their host, implying a slow rate of viral evolution and a large timescale of virus/host co-existence. Recent bio-informatic reports showed a large level of peptide homology between JCPyV and the human proteome. In this study, the antibody response to PyV peptides is evaluated. Methods: The in-silico analysis of the HPyV proteome was followed by peptide microarray serology. A HPyV-peptide microarray containing 4,284 peptides was designed and covered 10 polyomavirus proteomes. Plasma samples from 49 healthy subjects were tested against these peptides. Results: In-silico analysis of all possible HPyV 5-mer amino acid sequences were compared to the human proteome, and 1,609 unique motifs are presented. Assuming a linear epitope being as small as a pentapeptide, on average 9.3% of the polyomavirus proteome is unique and could be recognized by the host as non-self. Small t Ag (stAg) contains a significantly higher percentage of unique pentapeptides. Experimental evidence for the presence of antibodies against HPyV 15-mer peptides in healthy subjects resulted in the following observations: i) antibody responses against stAg were significantly elevated, and against viral protein 2 (VP2) significantly reduced; and ii) there was a significant correlation between the increasing number of embedded unique HPyV penta-peptides and the increase in microarray fluorescent signal.
    [Show full text]
  • Common Exposure to STL Polyomavirus During Childhood Efrem S
    Washington University School of Medicine Digital Commons@Becker Open Access Publications 2014 Common exposure to STL polyomavirus during childhood Efrem S. Lim Washington University School of Medicine in St. Louis Natalie M. Meinerz University of Colorado Boulder Blake Primi University of Colorado Boulder David Wang Washington University School of Medicine in St. Louis Robert L. Garcea University of Colorado Boulder Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Recommended Citation Lim, Efrem S.; Meinerz, Natalie M.; Primi, Blake; Wang, David; and Garcea, Robert L., ,"Common exposure to STL polyomavirus during childhood." Emerging Infectious Diseases.20,9. 1559-61. (2014). https://digitalcommons.wustl.edu/open_access_pubs/3541 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. persons ranges from 25% to 64%; all patients with Merkel Common cell carcinoma are seropositive (6,9). STLPyV was recently identified from fecal specimens Exposure to STL from a child in Malawi (10). Viral DNA also was detected in fecal specimens from the United States and The Gam- Polyomavirus bia, and STLPyV has been found in a surface-sanitized During Childhood skin wart surgically removed from the buttocks of a patient with a primary immunodeficiency called WHIM (warts, Efrem S. Lim, Natalie M. Meinerz, Blake Primi, hypogammaglobulinemia, infections, and myelokathexis) David Wang, and Robert L. Garcea syndrome (11). These observations suggest that STLPyV might infect humans. We defined the seropositivity rate of STL polyomavirus (STLPyV) was recently identified in STLPyV in humans using serum from 2 independent US human specimens.
    [Show full text]
  • Quantitative Detection of Human Malawi Polyomavirus in Nasopharyngeal Aspirates, Sera, and Feces in Beijing, China, Using Real-T
    Ma et al. Virology Journal (2017) 14:152 DOI 10.1186/s12985-017-0817-2 RESEARCH Open Access Quantitative detection of human Malawi polyomavirus in nasopharyngeal aspirates, sera, and feces in Beijing, China, using real- time TaqMan-based PCR Fen-lian Ma1, Dan-di Li1, Tian-li Wei2, Jin-song Li1 and Li-shu Zheng1* Abstract Background: Human Malawi polyomavirus (MWPyV) was discovered in 2012, but its prevalence and clinical characteristics are largely unknown. Methods: We used real-time TaqMan-based PCR to detect MWPyV in the feces (n = 174) of children with diarrhea, nasopharyngeal aspirates (n = 887) from children with respiratory infections, and sera (n = 200) from healthy adults, and analyzed its clinical characteristics statistically. All the MWPyV-positive specimens were also screened for other common respiratory viruses. Results: Sixteen specimens were positive for MWPyV, including 13 (1.47%) respiratory samples and three (1.7%) fecal samples. The samples were all co-infected with other respiratory viruses, most commonly with influenza viruses (69.2%) and human coronaviruses (30.7%). The MWPyV-positive children were diagnosed with bronchopneumonia or viral diarrhea. They ranged in age from 12 days to 9 years, and the most frequent symptoms were cough and fever. Conclusions: Real-time PCR is an effective tool for the detection of MWPyV in different types of samples. MWPyV infection mainly occurs in young children, and fecal–oral transmission is a possible route of its transmission. Keywords: Human Malawi polyomavirus (MWPyV), TaqMan real-time PCR, Nasopharyngeal aspirate, Feces, Respiratory virus Background (KIPyV and WUPyV), skin (MCPyV, HPyV6, HPyV7, The family Polyomaviridae contains small encapsidated and TSPyV), serum (HPyV9), stool samples (HPyV10 DNA viruses with a closed circular DNA genome of and isolates MW and MX, STLPyV), liver tissue ~5 kb, packaged within an icosahedral capsid structure.
    [Show full text]
  • Human Polyomavirus Type Six in Respiratory Samples From
    Zheng et al. Virology Journal (2015) 12:166 DOI 10.1186/s12985-015-0390-5 RESEARCH Open Access Human polyomavirus type six in respiratory samples from hospitalized children with respiratory tract infections in Beijing, China Wen-zhi Zheng1†, Tian-li Wei2†, Fen-lian Ma1, Wu-mei Yuan1, Qian Zhang1, Ya-xin Zhang2, Hong Cui2* and Li-shu Zheng1* Abstract Background: HPyV6 is a novel human polyomavirus (HPyV), and neither its natural history nor its prevalence in human disease is well known. Therefore, the epidemiology and phylogenetic status of HPyV6 must be systematically characterized. Methods: The VP1 gene of HPyV6 was detected with an established TaqMan real-time PCR from nasopharyngeal aspirate specimens collected from hospitalized children with respiratory tract infections. The HPyV6-positive specimens were screened for other common respiratory viruses with real-time PCR assays. Results: The prevalence of HPyV6 was 1.7 % (15/887), and children ≤ 5 years of age accounted for 80 % (12/15) of cases. All 15 HPyV6-positive patients were coinfected with other respiratory viruses, of which influenza virus A (IFVA) (8/15, 53.3 %) and respiratory syncytial virus (7/15, 46.7 %) were most common. All 15 HPyV6-positive patients were diagnosed with lower respiratory tract infections, and their viral loads ranged from 1.38 to 182.42 copies/μl nasopharyngeal aspirate specimen. The most common symptoms were cough (100 %) and fever (86.7 %). The complete 4926-bp genome (BJ376 strain, GenBank accession number KM387421) was amplified and showed 100 % identity to HPyV6 strain 607a. Conclusions: The prevalence of HPyV6 was 1.7 % in nasopharyngeal aspirate specimens from hospitalized children with respiratory tract infections, as analyzed by real-time PCR.
    [Show full text]
  • Fifty Years of JC Polyomavirus: a Brief Overview and Remaining Questions
    viruses Review Fifty Years of JC Polyomavirus: A Brief Overview and Remaining Questions Abigail L. Atkinson and Walter J. Atwood * Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA; [email protected] * Correspondence: [email protected] Received: 25 August 2020; Accepted: 30 August 2020; Published: 1 September 2020 Abstract: In the fifty years since the discovery of JC polyomavirus (JCPyV), the body of research representing our collective knowledge on this virus has grown substantially. As the causative agent of progressive multifocal leukoencephalopathy (PML), an often fatal central nervous system disease, JCPyV remains enigmatic in its ability to live a dual lifestyle. In most individuals, JCPyV reproduces benignly in renal tissues, but in a subset of immunocompromised individuals, JCPyV undergoes rearrangement and begins lytic infection of the central nervous system, subsequently becoming highly debilitating—and in many cases, deadly. Understanding the mechanisms allowing this process to occur is vital to the development of new and more effective diagnosis and treatment options for those at risk of developing PML. Here, we discuss the current state of affairs with regards to JCPyV and PML; first summarizing the history of PML as a disease and then discussing current treatment options and the viral biology of JCPyV as we understand it. We highlight the foundational research published in recent years on PML and JCPyV and attempt to outline which next steps are most necessary to reduce the disease burden of PML in populations at risk. Keywords: progressive multifocal leukoencephalopathy; JC polyomavirus; polyomavirus; HIV/AIDS; multiple sclerosis; autoimmune disease 1.
    [Show full text]
  • Common Exposure to STL Polyomavirus During Childhood
    persons ranges from 25% to 64%; all patients with Merkel Common cell carcinoma are seropositive (6,9). STLPyV was recently identified from fecal specimens Exposure to STL from a child in Malawi (10). Viral DNA also was detected in fecal specimens from the United States and The Gam- Polyomavirus bia, and STLPyV has been found in a surface-sanitized During Childhood skin wart surgically removed from the buttocks of a patient with a primary immunodeficiency called WHIM (warts, Efrem S. Lim, Natalie M. Meinerz, Blake Primi, hypogammaglobulinemia, infections, and myelokathexis) David Wang, and Robert L. Garcea syndrome (11). These observations suggest that STLPyV might infect humans. We defined the seropositivity rate of STL polyomavirus (STLPyV) was recently identified in STLPyV in humans using serum from 2 independent US human specimens. To determine seropositivity for STLPyV, sites (Denver, Colorado, and St. Louis, Missouri). we developed an ELISA and screened patient samples from 2 US cities (Denver, Colorado [500]; St. Louis, Mis- souri [419]). Overall seropositivity was 68%–70%. The age- The Study stratified data suggest that STLPyV infection is widespread To determine the seropositivity for STLPyV, we de- and commonly acquired during childhood. veloped a capture ELISA using recombinant glutathione S-transferase–tagged STLPyV VP1 capsomeres (on- line Technical Appendix, http://wwwnc.cdc.gov/EID/ olyomaviruses are nonenveloped double-stranded cir- article/20/9/14-0561-Techapp1.pdf). Electron microscopy Pcular DNA viruses that infect a wide range of hosts, of the STLPyV capsomeres showed 10-nm pentamers including humans. The capsid of the virus comprises pri- characteristic of polyomaviruses (Figure 1, panel A).
    [Show full text]
  • Age-Specific Seroprevalence of Human Polyomavirus 12 and Saint Louis
    Gaboriaud et al. Emerging Microbes & Infections (2018) 7:22 DOI 10.1038/s41426-018-0026-0 Emerging Microbes & Infections ARTICLE Open Access Age-specific seroprevalence of human polyomavirus 12 and Saint Louis and New Jersey polyomaviruses Pauline Gaboriaud1,MarionFerté1, Françoise Arnold1, Valérie Leblond1,JérômeNicol1,HeloïseDebare2, Mélanie Le Meur1, Fernanda Martini3,MauroTognon3 and Antoine Touzé1 Abstract The presence of specific antibodies against human polyomavirus 12, Saint Louis polyomavirus and New Jersey polyomavirus was investigated by using virus-like particle-based ELISAs with serum samples from 706 Italians aged 1- to 100-years-old. The findings indicate that these polyomaviruses circulate widely in humans, with peak seroprevalence, observed at adulthood, of 97.3%, 93.3%, 57.5%, for human polyomavirus 12, Saint Louis polyomavirus and New Jersey polyomavirus, respectively. Introduction about the natural history of these new human PyVs. The Seven new human polyomaviruses (PyVs) have been aim of this study was to investigate their age-specific identified since the discovery of Merkel cell polyomavirus seroprevalence in an Italian general population from the 1, 2 fi 1234567890():,; 1234567890():,; in 2008 . Three recently identi ed PyVs are human Ferrara region by using virus-like particle (VLP)-based polyomavirus 12 (HPyV12)3, Saint Louis polyomavirus ELISAs. (STLPyV)4 and New Jersey polyomavirus (NJPyV)5. STLPyV, classified as a Delta-polyomavirus6, was identi- Materials and methods fied in stools from a healthy Malawian child4. Previous Subjects and samples studies reported a seroprevalence of 68 to 70% and an Participants (n = 706; 416 females) ranged in age from early exposure in the United States7 as described for other 1- to 100-years-old.
    [Show full text]