Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency

Kantola, Kalle; Sadeghi, Mohammadreza; Lahtinen, Aira; Koskenvuo, Minna; Aaltonen, Leena‐Maija; Möttönen, Merja; Rahiala, Jaana; Saarinen‐Pihkala, Ulla M.; Riikonen, Pekka; Jartti, Tuomas; Ruuskanen, Olli; Söderlund‐Venermo, Maria; Hedman, Klaus

doi:10.1016/j.jcv.2009.04.008

Cited by 85 publications

(79 citation statements)

References 24 publications

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“…MCPyV has also been detected in tonsillar tissue, nasopharyngeal aspirates, and nasal swabs and thus could be spread by the respiratory route (2,15,16). MCC is a cutaneous cancer, and MCPyV has been recovered from normal skin of up to 40% of healthy adult volunteers, which would support cutaneous transmission of the virus (13,26).…”

Section: Discussionmentioning

confidence: 99%

Age-Specific Seroprevalence of Merkel Cell Polyomavirus, BK Virus, and JC Virus

Viscidi

Rollison

Sondak

et al. 2011

Clin. Vaccine Immunol.

165

146

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We produced capsids of Merkel cell polyomavirus (MCPyV) in a baculovirus expression system and developed a virus-like particle (VLP) enzyme-linked immunosorbent assay (ELISA). To determine age-specific seroprevalence, serum samples were collected from 947 individuals attending hospital outpatient clinics and ranging in age from 1 to 93 years. To evaluate the association between exposure to MCPyV and Merkel cell cancer (MCC), plasma samples were obtained from 33 MCC patients and 37 controls. MCPyV seroprevalence was 45% in children under 10 years of age, increased to 60% in the next decade of life, and peaked at 81% among those 60 to 69 years of age. Levels of MCPyV capsid antibodies were positively correlated with age (P ‫؍‬ 0.007). Virus specificity of MCPyV seroreactivity was supported by competitive inhibition of reactivity by MCPyV VLPs and not by BK polyomavirus (BKPyV) VLPs. MCPyV seroprevalence was greater among MCC patients (91%) than controls (68%; age-adjusted P value, 0.32); the mean level of MCPyV antibodies was also greater (P ‫؍‬ 0.04). The age-specific seroprevalence of MCPyV shares with previously known polyomaviruses, BKPyV and JC polyomavirus (JCPyV), evidence of widespread exposure in human populations beginning early in life. MCPyV age-specific seroprevalence also has unique features. Seroprevalence among children is higher than that of JCPyV but lower than that of BKPyV. Among older adults, MCPyV seroprevalence remains high, while that of BKPyV declines and that of JCPyV continues to rise. In agreement with results from other studies, we found an association between MCPyV seropositivity and MCC, and higher levels of serum MCPyV capsid antibodies in MCC patients than in controls.Merkel cell polyomavirus (MCPyV), a new human polyomavirus, was recently discovered by molecular techniques in Merkel cell carcinoma (MCC) (11), a rare and aggressive skin tumor (20,22). Studies from North America and Europe have detected MCPyV DNA by PCR in 69 to 100% of MCC tumors (1,9,11,13,14,17,25). The virus has also been detected in rare instances and in low copy numbers in cutaneous, gastrointestinal, and respiratory tract samples from healthy individuals (2,11,15). Little is known about the natural history of MCPyV infection in human populations. Serological assays can reveal the extent of past exposure to a virus and provide insights into its epidemiology. We and others have developed virus-like particle (VLP)-based enzyme-linked immunosorbent assays (ELISAs) to measure antibodies to various human and animal polyomaviruses (10, 27, 31). Polyomavirus VLPs are empty viral capsids produced by expression of the gene for the major capsid protein, VP1, in a eukaryotic expression system. VLPs resemble native virions morphologically and retain their immunological properties, including the ability to bind antiviral capsid antibodies. We now report the development of a VLP-based ELISA to detect antibodies to MCPyV and its application for comparison of the age-specific seroprevalence of MCPyV to those of two other huma...

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Section: Discussionmentioning

confidence: 99%

Age-Specific Seroprevalence of Merkel Cell Polyomavirus, BK Virus, and JC Virus

Viscidi

Rollison

Sondak

et al. 2011

Clin. Vaccine Immunol.

165

146

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“…Following this finding, other body compartments and specimen types have been screened: stool (6,17,23,(46)(47)(48), whole blood (45,48), plasma (18,49,50), serum (49), cerebrospinal fluid (51), lymphoid tissue (16,40,47), urine (6,7,48), and lung tissue (24,52). Detection rates of KIPyV and WUPyV in biological specimens are reported in Tables 1 and 2.…”

Section: Specimens Collectionmentioning

confidence: 99%

The human polyomaviruses KI and WU: virological background and clinical implications

Babakir‐Mina

Ciccozzi²,

Perno

et al. 2013

APMIS

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Babakir-Mina M, Ciccozzi M, Perno CF, Ciotti M. The human polyomaviruses KI and WU: virological background and clinical implications. APMIS 2013; 121: 746-54. In 2007, two novel polyomaviruses KI and WU were uncovered in the respiratory secretions of children with acute respiratory symptoms. Seroepidemiological studies showed that infection by these viruses is widespread in the human population. Following these findings, different biological specimens and body compartments have been screened by real-time PCR in the attempt to establish a pathogenetic role for KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in human diseases. Although both viruses have been found mainly in respiratory tract samples of immunocompromised patients, a clear causative link with the respiratory disease has not been established. Indeed, the lack of specific clinical or radiological findings, the frequent co-detection with other respiratory pathogens, the detection in subjects without signs or symptoms of respiratory disease, and the variability of the viral loads measured did not allow drawing a definitive conclusion. Prospective studies carried out on a large sample size including both immunocompromised and immunocompetent patients with and without respiratory symptoms are needed. Standardized quantitative real-time PCR methods, definition of a clear clinical cutoff value, timing in the collection of respiratory samples, are also crucial to understand the pathogenic role, if any, of KIPyV and WUPyV in human pathology.

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“…Little is known about the cell tropism of this virus, but viral sequences are predominantly found in respiratory tract secretions, with prevalence ranging between 0.5 and 6.5 % (Babakir-Mina et al, 2013). KIPyV DNA has occasionally been amplified from paranasal tissue (Babakir-Mina et al, 2009b), tonsil (Babakir-Mina et al, 2009b;Astegiano et al, 2010), lymphoid tissue (Sharp et al, 2009), lung tissue (Babakir-Mina et al, 2009c;Teramoto et al, 2011), stool (Allander et al, 2007;Babakir-Mina et al, 2009a;Bialasiewicz et al, 2009;Kantola et al, 2009;Mourez et al, 2009;Li et al, 2013), brain (Barzon et al, 2009b), eyebrow hair (Hampras et al, 2015), normal skin (Hampras et al, 2015) and blood and plasma (Barzon et al, 2009a;Babakir-Mina et al, 2010;Csoma et al, 2012;Touinssi et al, 2013). Immunohistochemical assay of spleen tissue from a 42-year-old human immunodeficiency virus (HIV)-positive male with a monoclonal antibody against the capsid protein VP1 of KIPyV stained positive, but the identity of the KIPyV VP1-positive cell type could not be determined (Siebrasse et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the non-coding control region of polyomavirus KI isolated from nasopharyngeal samples from patients with respiratory symptoms or infection and from blood from healthy blood donors in Norway

Song

Ghelue

Ludvigsen

et al. 2016

Journal of General Virology

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Seroepidemiological studies showed that the human polyomavirus KI (KIPyV) is common in the human population, with age-specific seroprevalence ranging from 40-90 %. Genome epidemiological analyses demonstrated that KIPyV DNA is predominantly found in respiratory tract samples of immunocompromised individuals and children suffering from respiratory diseases, but viral sequences have also been detected in brain, tonsil, lymphoid tissue studies, plasma, blood and faeces. Little is known about the sequence variation in the non-coding control region of KIPyV variants residing in different sites of the human body and whether specific strains dominate in certain parts of the world. In this study, we sequenced the non-coding control region (NCCR) of naturally occurring KIPyV variants in nasopharyngeal samples from patients with respiratory symptoms or infection and in blood from healthy donors in Norway. In total 86 sequences were obtained, 44 of which were identical to the original isolated Stockholm 60 variant. The remaining NCCRs contained one or several mutations, none of them previously reported. The same mutations were detected in NCCRs amplified from blood and nasopharyngeal samples. Some patients had different variants in their specimens. Transient transfection studies in HEK293 cells with a luciferase reporter plasmid demonstrated that some single mutations had a significant effect on the relative early and late promoter strength compared with the Stockholm 60 promoter. The effect of the NCCR mutations on viral replication and possible virulence properties remains to be established. INTRODUCTIONPolyomaviruses are non-enveloped viruses with a circular dsDNA genome of approximately 5000 bp. These viruses are common in birds and mammals, and recently the first complete fish polyomavirus genome has been published (Johne et al., 2011;Peretti et al., 2015). Their genome can †These authors contributed equally to this work.The GenBank/EMBL/DDBJ accession numbers for the sequences of the mutant NCCRs are KU564911-564952. ã 2016 The Authors Printed in Great Britain 1647Journal of General Virology (2016), 97, 1647-1657 DOI 10.1099 be divided into three functional regions: the early region, encoding regulatory proteins required for transcription and viral DNA replication; the late region, encoding the capsid proteins; and interspersed between these the non-coding control region (NCCR), encompassing the origin of replication and the promoters controlling transcription of the early and late genes, respectively (DeCaprio & Garcea, 2013). The first human polyomaviruses, BK and JC, were detected using histology or cytology followed by electron microscopy, and their existence was reported in 1971 (Gardner et al., 1971; Padgett et al., 1971). The development of new techniques such as high-throughput sequencing, rolling circle amplification and polymerase chain reaction with degenerate primers has led in recent years to the discovery of new polyomaviruses that can infect humans. KI polyomavirus, named after the researchers' instit...

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Merkel cell polyomavirus DNA in tumor-free tonsillar tissues and upper respiratory tract samples: Implications for respiratory transmission and latency

Cited by 85 publications

References 24 publications

Age-Specific Seroprevalence of Merkel Cell Polyomavirus, BK Virus, and JC Virus

Age-Specific Seroprevalence of Merkel Cell Polyomavirus, BK Virus, and JC Virus

The human polyomaviruses KI and WU: virological background and clinical implications

Characterization of the non-coding control region of polyomavirus KI isolated from nasopharyngeal samples from patients with respiratory symptoms or infection and from blood from healthy blood donors in Norway

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