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 HPyV 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. The mean number of PyV for which children were seropositive increased with the increasing of age: 4 standard deviations (SD) 1.8 in the 0–3-year group, 5 (SD 1.9) in the 4–7-year group, and 6 (SD 2.2) in the 8–17-year group. JC polyomavirus (JCPyV) DNA was detected in 1% of the adenoids, WUPyV in 12% of the tonsils, and 28% of the adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2% of the tonsils and adenoids, respectively. Our study gives new insights on the serological evidence of exposure to PyVs during childhood, and on their possible respiratory route of transmission.
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Allander T, Andreasson K, Gupta S, Bjerkner A, Bogdanovic G, Persson MA, Dalianis T, Ramqvist T, Andersson B (2007) Identification of a third human polyomavirus. J Virol 81(8):4130–4136. https://doi.org/10.1128/JVI.00028-07
Antonsson A, Green AC, Mallitt KA, O’Rourke PK, Pandeya N, Pawlita M, Waterboer T, Neale RE (2010) Prevalence and stability of antibodies to 37 human papillomavirus types—a population-based longitudinal study. Virology 407(1):26–32. https://doi.org/10.1016/j.virol.2010.07.046
Astegiano S, Terlizzi ME, Elia M, Cavallo GP, Costa C, Cavallo R, Bergallo M (2010) Prevalence of polyomaviruses BK, JC, SV40, KI, and WU in non-malignant tonsil specimens. Minerva Med 101(6):385–389
Bhattacharjee S, Chattaraj S (2017) Entry, infection, replication, and egress of human polyomaviruses: an update. Can J Microbiol 63(1):193–211. https://doi.org/10.1016/j.virol.2010.07.046
Brodsky L (1989) Modern assessment of tonsils and adenoids. Pediatr Clin N Am 36(6):1551–1569. https://doi.org/10.1016/S0031-3955(16)36806-7
Cason C, Campisciano G, Zanotta N, Valencic E, Delbue S, Bella R, Comar M (2016) SV40 infection of mesenchymal stromal cells from Wharton’s jelly drives the production of inflammatory and tumoral mediators. J Cell Physiol 232(11):3060–3066. https://doi.org/10.1002/jcp.25723
Chang H, Wang M, Tsai RT, Lin HS, Huan JS, Wang WC, Chang D (2002) High incidence of JC viruria in JC-seropositive older individuals. J Neuro-Oncol 8(5):447–451. https://doi.org/10.1080/13550280260422758
Chesters PM, Heritage J, McCance DJ (1983) Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues. J Infect Dis 147(4):676–684. https://doi.org/10.1093/infdis/147.4.676
Comar M, Delbue S, Zanotta N, Valencic E, Piscianz E, Del Savio R, Tesser A, Tommasini A, Ferrante P (2014a) In vivo detection of polyomaviruses JCV and SV40 in mesenchymal stem cells from human umbilical cords. Pediatr Blood Cancer 61(8):1347–1349. https://doi.org/10.1002/pbc.24943
Comar M, Zanotta N, Del Savio R, Vascotto F, Calabrese N, Zorat F, Pozzato G (2014b) No evidence of polyomavirus and EBV infections in Italian patients with mixed cryoglobulinemia infected chronically with HCV. J Med Virol 86(4):666–671. https://doi.org/10.1002/jmv.23867
DeCaprio JA, Garcea RL (2013) A cornucopia of human polyomaviruses. Nat Rev Microbiol 11(4):264–276. https://doi.org/10.1038/nrmicro2992
Delbue S, Tremolada S, Elia F, Carloni C, Amico S, Tavazzi E, Marchioni E, Novati S, Maserati R, Ferrante P (2010) Lymphotropic polyomavirus is detected in peripheral blood from immunocompromised and healthy subjects. J Clin Virol 47(2):156–160. https://doi.org/10.1016/j.jcv.2009.11.029
Doerries K (2006) Human polyomavirus JC and BK persistent infection. Adv Exp Med Biol 577:102–116. https://doi.org/10.1007/0-387-32957-9_8
Elia F, Villani S, Ambrogi F, Signorini L, Dallari S, Binda S, Primache V, Pellegrinelli L, Ferrante P, Delbue S (2017) JC virus infection is acquired very early in life: evidence from a longitudinal serological study. J Neuro-Oncol 23(1):99–105. https://doi.org/10.1007/s13365-016-0477-9
Feng H, Shuda M, Chang Y, Moore PS (2008) Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319(5866):1096–1100. https://doi.org/10.1126/science.1152586
Gardner SD, Field AM, Coleman DV, Hulme B (1971) New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet 1(7712):1253–1257
Garren SB, Kondaveeti Y, Duff MO, Carmichael GG (2015) Global analysis of mouse polyomavirus infection reveals dynamic regulation of viral and host gene expression and promiscuous viral RNA editing. PLoS Pathog 11(9):e1005166. https://doi.org/10.1371/journal.ppat.1005166
Gaynor AM, Nissen MD, Whiley DM, Mackay IM, Lambert SB, Wu G, Brennan DC, Storch GA, Sloots TP, Wang D (2007) Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog 3(5):e64. https://doi.org/10.1371/journal.ppat.0030064
Gheit T, Dutta S, Oliver J, Robitaille A, Hampras S, Combes JD, McKay-Chopin S, Le Calvez-Kelm F, Fenske N, Cherpelis B, Giuliano AR, Franceschi S, McKay J, Rollison DE, Tommasino M (2017) Isolation and characterization of a novel putative human polyomavirus. Virology 506:45–54. https://doi.org/10.1016/j.virol.2017.03.007
Goh S, Lindau C, Tiveljung-Lindell A, Allander T (2009) Merkel cell polyomavirus in respiratory tract secretions. Emerg Infect Dis 15(3):489–491. https://doi.org/10.3201/eid1503.081206
Gossai A, Waterboer T, Nelson HH, Michel A, Willhauck-Fleckenstein M, Farzan SF, Hoen AG, Christensen BC, Kelsey KT, Marsit CJ, Pawlita M, Karagas MR (2016) Seroepidemiology of human polyomaviruses in a US population. Am J Epidemiol 183(1):61–69. https://doi.org/10.1093/aje/kwv155
Hennes EM, Kornek B, Huppke P, Reindl M, Rostasy K, Berger T (2016) Age-dependent seroprevalence of JCV antibody in children. Neuropediatrics 47(02):112–114. https://doi.org/10.1055/s-0035-1565272
Herberhold S, Hellmich M, Panning M, Bartok E, Silling S, Akgul B, Wieland U (2017) Human polyomavirus and human papillomavirus prevalence and viral load in non-malignant tonsillar tissue and tonsillar carcinoma. Med Microbiol Immunol 206(2):93–103. https://doi.org/10.1007/s00430-016-0486-6
Imperiale MJ (2000) The human polyomaviruses, BKV and JCV: molecular pathogenesis of acute disease and potential role in cancer. Virology 267(1):1–7. https://doi.org/10.1006/viro.1999.0092
Kantola K, Sadeghi M, Lahtinen A, Koskenvuo M, Aaltonen LM, Mottonen M, Rahiala J, Saarinen-Pihkala U, Riikonen P, Jartti T, Ruuskanen O, Soderlund-Venermo M, Hedman K (2009) Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: implications for respiratory transmission and latency. J Clin Virol 45(4):292–295. https://doi.org/10.1016/j.jcv.2009.04.008
Karagas MR, Nelson HH, Sehr P, Waterboer T, Stukel TA, Andrew A, Green AC, Bavinck JN, Perry A, Spencer S, Rees JR, Mott LA, Pawlita M (2006) Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst 98(6):389–395. https://doi.org/10.1093/jnci/djj092
Kean JM, Rao S, Wang M, Garcea RL (2009) Seroepidemiology of human polyomaviruses. PLoS Pathog 5(3):e1000363. https://doi.org/10.1371/journal.ppat.1000363
Khalili K, Del Valle L, Otte J, Weaver M, Gordon J (2003) Human neurotropic polyomavirus, JCV, and its role in carcinogenesis. Oncogene 22(33):5181–5191. https://doi.org/10.1038/sj.onc.1206559
Kjaerheim K, Roe OD, Waterboer T, Sehr P, Rizk R, Dai HY, Sandeck H, Larsson E, Andersen A, Boffetta P, Pawlita M (2007) Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples. Int J Cancer 120(11):2459–2465. https://doi.org/10.1002/ijc.22592
Korup S, Rietscher J, Calvignac-Spencer S, Trusch F, Hofmann J, Moens U, Sauer I, Voigt S, Schmuck R, Ehlers B (2013) Identification of a novel human polyomavirus in organs of the gastrointestinal tract. PLoS One 8(3):e58021. https://doi.org/10.1371/journal.pone.0058021
Lim ES, Reyes A, Antonio M, Saha D, Ikumapayi UN, Adeyemi M, Stine OC, Skelton R, Brennan DC, Mkakosya RS, Manary MJ, Gordon JI, Wang D (2013) Discovery of STL polyomavirus, a polyomavirus of ancestral recombinant origin that encodes a unique T antigen by alternative splicing. Virology 436(2):295–303. https://doi.org/10.1016/j.virol.2012.12.005
Malhotra J, Waterboer T, Pawlita M, Michel A, Cai Q, Zheng W, Gao YT, Lan Q, Rothman N, Langseth H, Grimsrud TK, Yuan JM, Koh WP, Wang R, Arslan AA, Zeleniuch-Jacquotte A, Boffetta P (2016) Serum biomarkers of polyomavirus infection and risk of lung cancer in never smokers. Br J Cancer 115(9):1131–1139. https://doi.org/10.1038/bjc.2016.285
Martel-Jantin C, Pedergnana V, Nicol JT, Leblond V, Tregouet DA, Tortevoye P, Plancoulaine S, Coursaget P, Touze A, Abel L, Gessain A (2013) Merkel cell polyomavirus infection occurs during early childhood and is transmitted between siblings. J Clin Virol 58(1):288–291. https://doi.org/10.1016/j.jcv.2013.06.004
Martel-Jantin C, Filippone C, Tortevoye P, Afonso PV, Betsem E, Descorps-Declere S, Nicol JT, Touze A, Coursaget P, Crouzat M, Berthet N, Cassar O, Gessain A (2014) Molecular epidemiology of merkel cell polyomavirus: evidence for geographically related variant genotypes. J Clin Microbiol 52(5):1687–1690. https://doi.org/10.1128/JCM.02348-13
Maximova N, Granzotto M, Kiren V, Zanon D, Comar M (2013) First description of Merkel cell polyomavirus DNA detection in a patient with Stevens-Johnson syndrome. J Med Virol 85(5):918–923. https://doi.org/10.1002/jmv.23550
van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC (2010) Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Pathog 6(7):e1001024. https://doi.org/10.1371/journal.ppat.1001024
Michael KM, Waterboer T, Sehr P, Rother A, Reidel U, Boeing H, Bravo IG, Schlehofer J, Gartner BC, Pawlita M (2008) Seroprevalence of 34 human papillomavirus types in the German general population. PLoS Pathog 4(6):e1000091. https://doi.org/10.1371/journal.ppat.1000091
Miller MA, Weibel C, Kahn JS, Andiman WA (2012) Seroepidemiology of WU polyomavirus among children exposed perinatally to HIV-1. J Med Virol 84(2):188–193. https://doi.org/10.1002/jmv.23189
Mishra N, Pereira M, Rhodes RH, An P, Pipas JM, Jain K, Kapoor A, Briese T, Faust PL, Lipkin WI (2014) Identification of a novel polyomavirus in a pancreatic transplant recipient with retinal blindness and vasculitic myopathy. J Infect Dis 210(10):1595–1599. https://doi.org/10.1093/infdis/jiu250
Nicol JT, Touze A, Robinot R, Arnold F, Mazzoni E, Tognon M, Coursaget P (2012) Seroprevalence and cross-reactivity of human polyomavirus 9. Emerg Infect Dis 18(8):1329–1332. https://doi.org/10.3201/eid1808.111625
Nicol JT, Robinot R, Carpentier A, Carandina G, Mazzoni E, Tognon M, Touze A, Coursaget P (2013) Age-specific seroprevalences of merkel cell polyomavirus, human polyomaviruses 6, 7, and 9, and trichodysplasia spinulosa-associated polyomavirus. Clin Vaccine Immunol 20(3):363–368. https://doi.org/10.1128/CVI.00438-12
Nicol JT, Leblond V, Arnold F, Guerra G, Mazzoni E, Tognon M, Coursaget P, Touze A (2014) Seroprevalence of human Malawi polyomavirus. J Clin Microbiol 52(1):321–323. https://doi.org/10.1128/JCM.02730-13
Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH (1971) Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1(7712):1257–1260
Papa N, Zanotta N, Knowles A, Orzan E, Comar M (2016) Detection of Malawi polyomavirus sequences in secondary lymphoid tissues from Italian healthy children: a transient site of infection. Virol J 13(1):97. https://doi.org/10.1186/s12985-016-0553-z
Patel NC, Vilchez RA, Killen DE, Zanwar P, Sroller V, Eldin KW, López-Terrada D, Butel JS (2008) Detection of polyomavirus SV40 in tonsils from immunocompetent children. J Clin Virol 43(1):66–72. https://doi.org/10.1016/j.jcv.2008.04.011
Sadeghi M, Aaltonen LM, Hedman L, Chen T, Soderlund-Venermo M, Hedman K (2014) Detection of TS polyomavirus DNA in tonsillar tissues of children and adults: evidence for site of viral latency. J Clin Virol 59(1):55–58. https://doi.org/10.1016/j.jcv.2013.11.008
Sadeghi M, Wang Y, Ramqvist T, Aaltonen LM, Pyöriä L, Toppinen M, Söderlund-Venermo M, Hedman K (2017) Multiplex detection in tonsillar tissue of all known human polyomaviruses. BMC Infect Dis 17(1):409. https://doi.org/10.1186/s12879-017-2479-5
Salakova M, Koslabova E, Vojtechova Z, Tachezy R, Sroller V (2016) Detection of human polyomaviruses MCPyV, HPyV6, and HPyV7 in malignant and non-malignant tonsillar tissues. J Med Virol 88(4):695–702. https://doi.org/10.1002/jmv.24385
Schowalter RM, Pastrana DV, Pumphrey KA, Moyer AL, Buck CB (2010) Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 7(6):509–515. https://doi.org/10.1016/j.chom.2010.05.006
Scuda N, Hofmann J, Calvignac-Spencer S, Ruprecht K, Liman P, Kuhn J, Hengel H, Ehlers B (2011) A novel human polyomavirus closely related to the african green monkey-derived lymphotropic polyomavirus. J Virol 85(9):4586–4590. https://doi.org/10.1128/JVI.02602-10
Siebrasse EA, Reyes A, Lim ES, Zhao G, Mkakosya RS, Manary MJ, Gordon JI, Wang D (2012) Identification of MW polyomavirus, a novel polyomavirus in human stool. J Virol 86(19):10321–10326. https://doi.org/10.1128/JVI.01210-12
Signorini L, Belingheri M, Ambrogi F, Pagani E, Binda S, Ticozzi R, Ferraresso M, Ghio L, Giacon B, Ferrante P, Delbue S (2014) High frequency of Merkel cell polyomavirus DNA in the urine of kidney transplant recipients and healthy controls. J Clin Virol 61(4):565–570. https://doi.org/10.1016/j.jcv.2014.10.012
Sourvinos G, Mammas IN, Spandidos DA (2015) Merkel cell polyomavirus infection in childhood: current advances and perspectives. Arch Virol 160(4):887–892. https://doi.org/10.1007/s00705-015-2343-0
Sroller V, Hamsikova E, Ludvikova V, Vochozkova P, Kojzarova M, Fraiberk M, Salakova M, Moravkova A, Forstova J, Nemeckova S (2014) Seroprevalence rates of BKV, JCV, and MCPyV polyomaviruses in the general Czech Republic population. J Med Virol 86(9):1560–1568. https://doi.org/10.1002/jmv.23841
Sroller V, Hamsikova E, Ludvikova V, Musil J, Nemeckova S, Salakova M (2016) Seroprevalence rates of HPyV6, HPyV7, TSPyV, HPyV9, MWPyV and KIPyV polyomaviruses among the healthy blood donors. J Med Virol 88(7):1254–1261. https://doi.org/10.1002/jmv.24440
Stolt A, Sasnauskas K, Koskela P, Lehtinen M, Dillner J (2003) Seroepidemiology of the human polyomaviruses. J Gen Virol 84(6):1499–1504. https://doi.org/10.1099/vir.0.18842-0
Taronna A, Mazzoni E, Corallini A, Bononi I, Pietrobon S, Guerra G, Palmonari C, Borgna-Pignatti C, Comar M, Bovenzi M, Casali F, Marci R, Rezza G, Barbanti-Brodano G, Tognon M, Martini F (2013) Serological evidence of an early seroconversion to simian virus 40 in healthy children and adolescents. PLoS One 8(4):e61182. https://doi.org/10.1371/journal.pone.0061182
Trusch F, Klein M, Finsterbusch T, Kühn J, Hofmann J, Ehlers B (2012) Seroprevalence of human polyomavirus 9 and cross-reactivity to African green monkey-derived lymphotropic polyomavirus. J Gen Virol 93(Pt_4):698–705. https://doi.org/10.1099/vir.0.039156-0
Viscidi RP, Rollison DE, Sondak VK, Silver B, Messina JL, Giuliano AR, Fulp W, Ajidahun A, Rivanera D (2011) Age-specific seroprevalence of Merkel cell polyomavirus, BK virus, and JC virus. Clin Vaccine Immunol 18(10):1737–1743. https://doi.org/10.1128/CVI.05175-11
Waterboer T, Sehr P, Pawlita M (2006) Suppression of non-specific binding in serological Luminex assays. J Immunol Methods 309(1-2):200–204. https://doi.org/10.1016/j.jim.2005.11.008
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The study was supported by Italian Ministry of Health, contract grant number R.C. 11/2011.
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The study was approved by the Institutional Scientific Board of the Institute for Maternal and Child Health—IRCCS “Burlo Garofolo” (Trieste) and by the local independent Ethics Committee. Parental written informed consent was obtained for each participant in accordance with the principles outlined in the Declaration of Helsinki.
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Cason, C., Monasta, L., Zanotta, N. et al. Antibody response to polyomavirus primary infection: high seroprevalence of Merkel cell polyomavirus and lymphoid tissue involvement. J. Neurovirol. 24, 314–322 (2018). https://doi.org/10.1007/s13365-017-0612-2
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DOI: https://doi.org/10.1007/s13365-017-0612-2