Polyomavirus infections in humans

Annika Lundstig

Polyomavirus infections in humans

Annika Lundstig

Klinisk mikrobiologi, Malmö

Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

Sammanfattning

Popular Abstract in Swedish
Polyomavirus är en familj av små DNA-virus som har onkogena egenskaper i försöksdjur i celler in vitro. De humana polyomavirusen BK virus (BKV) och JC virus (JCV) infekterar en stor del av befolkningen. Ungefär 70-80 % av vuxna är seropositiva, har antikroppar mot BKV och JCV. Primär infektion inträffar oftast under barndomen och är ofta subklinisk. Efter primära infektionen blir viruset latent i kroppen och kan reaktiveras och orsaka sjukdom vid alvarlig immunsuppresion som leukemi, njurtransplantation och AIDS. BK virus är mest relaterat till urinvägs infektioner och JC virus orsakar progressiv multifokal leukoencefalopati (PML), en sjukdom som drabbar hjärnan.

Simian virus 40 (SV40) är ursprungligen ett apvirus som förekom som förorening i poliovaccin på 1960-talet och har sedan dess ibland rapporterats förekomma hos människa. Samband mellan polyomavirus och vissa former av cancer har rapporterats.

Vi har grundligt utvecklat och validerat serologisk metodik för specifik påvisning av antikroppar samt metodik för kvantifiering av genomet med Realtids-PCR för BK, JC och SV40. Med hjälp av dessa metoder genomfört storskalig biobanks-baserade studier, först av förekomsten av polyomavirus infektioner i en svensk population, samt sedan utfört prospektiva epidemiologiska studier för att undersöka v om polyomavirus-infektion ökar risken för cancer vid långtidsuppföljning.

Både BK och JC är vanliga i Sverige. Epidemiologin skiljer sig åt, då BK virus infektion är vanligare än JC infektion. Infektion med BK virus inträffar vid tidigare ålder än med JC virus. Sju procent av en normalbefolkning befanns ha SV40-specifika antikroppar, men inga SV40genom kunde påvisas i den tumör som oftast rapporterats vara SV0-positiv (mesoteliom). JC och BK infektion innebär inte någon ökad risk för neuroblastom eller kolorektal cancer, vilket tidigare hade hävdats.

Moderna och välvaliderade metoder för mätning av förekomsten av antikroppar i serum mot polyomavirus och påvisning av själva viruset i humana prover har etablerats. Vi har fått kännedom om prevalens och åldersspecifik förekomst av BK, JC och SV40-infektioner i Sverige. Vi har inte kunnat bekräfta tidigare rapporter om att infektion av polyomavirus skulle orsaka cancer.

Originalspråk	engelska
Kvalifikation	Doktor
Tilldelande institution	Klinisk mikrobiologi, Malmö
Handledare	Dillner, Joakim, handledare
Tilldelningsdatum	2007 okt. 23
Förlag	Department of Medical Microbiology, Lund University
ISBN (tryckt)	978-91-85897-08-7
Status	Published - 2007

Bibliografisk information

Defence details

Date: 2007-10-23
Time: 10:00
Place: Patologens föreläsningssal, Universitetsjukhuset UMAS, Malmö, ingång 78

External reviewer(s)

Name: Dalianis, Tina
Title: Professor
Affiliation: Institutionen för Onkologi-Patologi

---

<div class="article_info">A Stolt, K Sasnauskas, P Koskela, M Lehtinen and J Dillner. <span class="article_issue_date">2003</span>. <span class="article_title">Seroepidemiology of the human polyomaviruses.</span> <span class="journal_series_title">J Gen Virol</span>, <span class="journal_volume">vol 84</span> <span class="journal_pages">pp 1499-504</span>.</div>
<div class="article_info">A Stolt, M Kjellin, K Sasnauskas, T Luostarinen, P Koskela, M Lehtinen and J Dillner. <span class="article_issue_date">2005</span>. <span class="article_title">Maternal human polyomavirus infection and risk of neuroblastoma in the child.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 20</span> <span class="journal_pages">pp 393-6</span>.</div>
<div class="article_info">A Lundstig, P Stattin, K Persson, K Sasnauskas, RP Viscidi, RE Gislefoss and J Dillner. <span class="article_issue_date">2007</span>. <span class="article_title">No excess risk for colorectal cancer among subjects seropositive for the JC Polyomavirus.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 10</span> <span class="journal_pages">pp 1098-102</span>.</div>
<div class="article_info">A Lundstig, L Eliasson, M Lehtinen, K Sasnauskas, P Koskela and J Dillner. <span class="article_issue_date">2005</span>. <span class="article_title">Prevalence and stability of human serum antibodies to Simian virus 40 VP1 virus-like particles.</span> <span class="journal_series_title">J Gen Virol</span>, <span class="journal_volume">vol 86</span> <span class="journal_pages">pp 1703-8</span>.</div>
<div class="article_info">. <span class="article_issue_date"></span>. <span class="article_title">No detection of SV40 DNA in mesothelioma tissues from a high incidence area in Sweden.</span> <span class="journal_series_title">Anticancer Res</span>, (accepted)</div>
<div class="article_info">A Lundstig, A Dejmek, C Eklund, I Filinic and J Dillner. <span class="article_issue_date"></span>. <span class="article_title">No detection of SV40 DNA in mesothelioma tissues from a high incidence area in Sweden.</span> <span class="journal_series_title">Anticancer Res</span>, (accepted)</div>

Ämnesklassifikation (UKÄ)

Mikrobiologi inom det medicinska området

FN:s Globala mål

Denna forskningsoutput relaterar till följande Globala mål

Citera det här

@phdthesis{5823a358b79c4527a31a17970652d1e5,

title = "Polyomavirus infections in humans",

abstract = "The human polyomaviruses BKV and JCV are endemic and infect > 70% of population worldwide. Primary infections occur during childhood and are largely subclinical. Following primary infection, both viruses persist as latent infections in the kidneys and B lymphocytes. Under conditions of severe immunosuppression like leukaemia, organ transplantation and AIDS, the viruses can reactivate and cause diseases. BKV is mainly related to urinary tract diseases and JCV is the causative agent of progressive multifocal leukoencephalopathy (PML). The human polyomaviruses have oncogenic potential and a possible association of with human cancer has been reported. JCV has been detected in certain brain tumours, in particular oligoastrocytoma and BKV has been detected in a variety of tumours, including neuroblastoma. Simian virus 40 (SV40), of rhesus monkey origin was accidentally introduced to humans through contaminated polio vaccine. Several studies have detected SV40 sequences in human tumours, mainly mesothelioma, osteosarcoma, ependymomas and choroid plexus tumours. The aim of the thesis was to study the infections of polyomaviruses in humans and their role in human cancers. We have established a VLP-based EIA BKV, JCV and SV40. Sera from Swedish children showed that BKV and JCV increased by age. Seropositivity was generally stable over time in serial samples. Analysis of maternal sera using both serology and DNA detection, found no evidence for association between BKV or JCV infection during pregnancy and an increased risk of developing neuroblastoma in the child. Sera from 386 cases of colorectal cancer and controls were investigated for JCV and BKV IgG seropositivity. The serologic assay used was validated within the study and found to have very high sensitivity for detecting subjects with polyoma virus shedding. Our study found no evidence for association between infection with the human polyomaviruses and excess risk for colorectal cancer. A low prevalence (7.6%) of SV40-specific antibodies was detected in the Nordic population. None of the SV40-seropositive samples contained detectable SV40 DNA. The investigation of 28 malignant mesothelioma tissues from deceased patients in Sweden found no detectable SV40 DNA. In summary, modern assays to detect polyomavirus antibodies and DNA has been established. We have now knowledge of the presence and age-specific prevalence of BKV, JCV and SV40 in Nordic countries. We did not confirm any association between infection with polyomaviruses and cancer.",

keywords = "Polyomaviruses, tumour virology, BK virus, neuroblastoma, maternal infection, Real Time PCR, enzyme immunoassay, seroprevalence, JC virus, SV40, virus like particles (VLPs), seroepidemiology, biobank, mesothelioma tissues, Microbiology, bacteriology, virology, mycology, Mikrobiologi, bakteriologi, virologi, mykologi",

author = "Annika Lundstig",

note = "Defence details Date: 2007-10-23 Time: 10:00 Place: Patologens f{\"o}rel{\"a}sningssal, Universitetsjukhuset UMAS, Malm{\"o}, ing{\aa}ng 78 External reviewer(s) Name: Dalianis, Tina Title: Professor Affiliation: Institutionen f{\"o}r Onkologi-Patologi --- <div class={"}article_info{"}>A Stolt, K Sasnauskas, P Koskela, M Lehtinen and J Dillner. <span class={"}article_issue_date{"}>2003</span>. <span class={"}article_title{"}>Seroepidemiology of the human polyomaviruses.</span> <span class={"}journal_series_title{"}>J Gen Virol</span>, <span class={"}journal_volume{"}>vol 84</span> <span class={"}journal_pages{"}>pp 1499-504</span>.</div> <div class={"}article_info{"}>A Stolt, M Kjellin, K Sasnauskas, T Luostarinen, P Koskela, M Lehtinen and J Dillner. <span class={"}article_issue_date{"}>2005</span>. <span class={"}article_title{"}>Maternal human polyomavirus infection and risk of neuroblastoma in the child.</span> <span class={"}journal_series_title{"}>Int J Cancer</span>, <span class={"}journal_volume{"}>vol 20</span> <span class={"}journal_pages{"}>pp 393-6</span>.</div> <div class={"}article_info{"}>A Lundstig, P Stattin, K Persson, K Sasnauskas, RP Viscidi, RE Gislefoss and J Dillner. <span class={"}article_issue_date{"}>2007</span>. <span class={"}article_title{"}>No excess risk for colorectal cancer among subjects seropositive for the JC Polyomavirus.</span> <span class={"}journal_series_title{"}>Int J Cancer</span>, <span class={"}journal_volume{"}>vol 10</span> <span class={"}journal_pages{"}>pp 1098-102</span>.</div> <div class={"}article_info{"}>A Lundstig, L Eliasson, M Lehtinen, K Sasnauskas, P Koskela and J Dillner. <span class={"}article_issue_date{"}>2005</span>. <span class={"}article_title{"}>Prevalence and stability of human serum antibodies to Simian virus 40 VP1 virus-like particles.</span> <span class={"}journal_series_title{"}>J Gen Virol</span>, <span class={"}journal_volume{"}>vol 86</span> <span class={"}journal_pages{"}>pp 1703-8</span>.</div> <div class={"}article_info{"}>. <span class={"}article_issue_date{"}></span>. <span class={"}article_title{"}>No detection of SV40 DNA in mesothelioma tissues from a high incidence area in Sweden.</span> <span class={"}journal_series_title{"}>Anticancer Res</span>, (accepted)</div> <div class={"}article_info{"}>A Lundstig, A Dejmek, C Eklund, I Filinic and J Dillner. <span class={"}article_issue_date{"}></span>. <span class={"}article_title{"}>No detection of SV40 DNA in mesothelioma tissues from a high incidence area in Sweden.</span> <span class={"}journal_series_title{"}>Anticancer Res</span>, (accepted)</div>",

year = "2007",

language = "English",

isbn = "978-91-85897-08-7",

series = "Lund University Faculty of Medicine Doctoral Dissertation Series ",

publisher = "Department of Medical Microbiology, Lund University",

type = "Doctoral Thesis (compilation)",

school = "Clinical Microbiology, Malm{\"o}",

}

TY - THES

T1 - Polyomavirus infections in humans

AU - Lundstig, Annika

N1 - Defence details Date: 2007-10-23 Time: 10:00 Place: Patologens föreläsningssal, Universitetsjukhuset UMAS, Malmö, ingång 78 External reviewer(s) Name: Dalianis, Tina Title: Professor Affiliation: Institutionen för Onkologi-Patologi --- <div class="article_info">A Stolt, K Sasnauskas, P Koskela, M Lehtinen and J Dillner. <span class="article_issue_date">2003</span>. <span class="article_title">Seroepidemiology of the human polyomaviruses.</span> <span class="journal_series_title">J Gen Virol</span>, <span class="journal_volume">vol 84</span> <span class="journal_pages">pp 1499-504</span>.</div> <div class="article_info">A Stolt, M Kjellin, K Sasnauskas, T Luostarinen, P Koskela, M Lehtinen and J Dillner. <span class="article_issue_date">2005</span>. <span class="article_title">Maternal human polyomavirus infection and risk of neuroblastoma in the child.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 20</span> <span class="journal_pages">pp 393-6</span>.</div> <div class="article_info">A Lundstig, P Stattin, K Persson, K Sasnauskas, RP Viscidi, RE Gislefoss and J Dillner. <span class="article_issue_date">2007</span>. <span class="article_title">No excess risk for colorectal cancer among subjects seropositive for the JC Polyomavirus.</span> <span class="journal_series_title">Int J Cancer</span>, <span class="journal_volume">vol 10</span> <span class="journal_pages">pp 1098-102</span>.</div> <div class="article_info">A Lundstig, L Eliasson, M Lehtinen, K Sasnauskas, P Koskela and J Dillner. <span class="article_issue_date">2005</span>. <span class="article_title">Prevalence and stability of human serum antibodies to Simian virus 40 VP1 virus-like particles.</span> <span class="journal_series_title">J Gen Virol</span>, <span class="journal_volume">vol 86</span> <span class="journal_pages">pp 1703-8</span>.</div> <div class="article_info">. <span class="article_issue_date"></span>. <span class="article_title">No detection of SV40 DNA in mesothelioma tissues from a high incidence area in Sweden.</span> <span class="journal_series_title">Anticancer Res</span>, (accepted)</div> <div class="article_info">A Lundstig, A Dejmek, C Eklund, I Filinic and J Dillner. <span class="article_issue_date"></span>. <span class="article_title">No detection of SV40 DNA in mesothelioma tissues from a high incidence area in Sweden.</span> <span class="journal_series_title">Anticancer Res</span>, (accepted)</div>

PY - 2007

Y1 - 2007

N2 - The human polyomaviruses BKV and JCV are endemic and infect > 70% of population worldwide. Primary infections occur during childhood and are largely subclinical. Following primary infection, both viruses persist as latent infections in the kidneys and B lymphocytes. Under conditions of severe immunosuppression like leukaemia, organ transplantation and AIDS, the viruses can reactivate and cause diseases. BKV is mainly related to urinary tract diseases and JCV is the causative agent of progressive multifocal leukoencephalopathy (PML). The human polyomaviruses have oncogenic potential and a possible association of with human cancer has been reported. JCV has been detected in certain brain tumours, in particular oligoastrocytoma and BKV has been detected in a variety of tumours, including neuroblastoma. Simian virus 40 (SV40), of rhesus monkey origin was accidentally introduced to humans through contaminated polio vaccine. Several studies have detected SV40 sequences in human tumours, mainly mesothelioma, osteosarcoma, ependymomas and choroid plexus tumours. The aim of the thesis was to study the infections of polyomaviruses in humans and their role in human cancers. We have established a VLP-based EIA BKV, JCV and SV40. Sera from Swedish children showed that BKV and JCV increased by age. Seropositivity was generally stable over time in serial samples. Analysis of maternal sera using both serology and DNA detection, found no evidence for association between BKV or JCV infection during pregnancy and an increased risk of developing neuroblastoma in the child. Sera from 386 cases of colorectal cancer and controls were investigated for JCV and BKV IgG seropositivity. The serologic assay used was validated within the study and found to have very high sensitivity for detecting subjects with polyoma virus shedding. Our study found no evidence for association between infection with the human polyomaviruses and excess risk for colorectal cancer. A low prevalence (7.6%) of SV40-specific antibodies was detected in the Nordic population. None of the SV40-seropositive samples contained detectable SV40 DNA. The investigation of 28 malignant mesothelioma tissues from deceased patients in Sweden found no detectable SV40 DNA. In summary, modern assays to detect polyomavirus antibodies and DNA has been established. We have now knowledge of the presence and age-specific prevalence of BKV, JCV and SV40 in Nordic countries. We did not confirm any association between infection with polyomaviruses and cancer.

AB - The human polyomaviruses BKV and JCV are endemic and infect > 70% of population worldwide. Primary infections occur during childhood and are largely subclinical. Following primary infection, both viruses persist as latent infections in the kidneys and B lymphocytes. Under conditions of severe immunosuppression like leukaemia, organ transplantation and AIDS, the viruses can reactivate and cause diseases. BKV is mainly related to urinary tract diseases and JCV is the causative agent of progressive multifocal leukoencephalopathy (PML). The human polyomaviruses have oncogenic potential and a possible association of with human cancer has been reported. JCV has been detected in certain brain tumours, in particular oligoastrocytoma and BKV has been detected in a variety of tumours, including neuroblastoma. Simian virus 40 (SV40), of rhesus monkey origin was accidentally introduced to humans through contaminated polio vaccine. Several studies have detected SV40 sequences in human tumours, mainly mesothelioma, osteosarcoma, ependymomas and choroid plexus tumours. The aim of the thesis was to study the infections of polyomaviruses in humans and their role in human cancers. We have established a VLP-based EIA BKV, JCV and SV40. Sera from Swedish children showed that BKV and JCV increased by age. Seropositivity was generally stable over time in serial samples. Analysis of maternal sera using both serology and DNA detection, found no evidence for association between BKV or JCV infection during pregnancy and an increased risk of developing neuroblastoma in the child. Sera from 386 cases of colorectal cancer and controls were investigated for JCV and BKV IgG seropositivity. The serologic assay used was validated within the study and found to have very high sensitivity for detecting subjects with polyoma virus shedding. Our study found no evidence for association between infection with the human polyomaviruses and excess risk for colorectal cancer. A low prevalence (7.6%) of SV40-specific antibodies was detected in the Nordic population. None of the SV40-seropositive samples contained detectable SV40 DNA. The investigation of 28 malignant mesothelioma tissues from deceased patients in Sweden found no detectable SV40 DNA. In summary, modern assays to detect polyomavirus antibodies and DNA has been established. We have now knowledge of the presence and age-specific prevalence of BKV, JCV and SV40 in Nordic countries. We did not confirm any association between infection with polyomaviruses and cancer.

KW - Polyomaviruses

KW - tumour virology

KW - BK virus

KW - neuroblastoma

KW - maternal infection

KW - Real Time PCR

KW - enzyme immunoassay

KW - seroprevalence

KW - JC virus

KW - SV40

KW - virus like particles (VLPs)

KW - seroepidemiology

KW - biobank

KW - mesothelioma tissues

KW - Microbiology

KW - bacteriology

KW - virology

KW - mycology

KW - Mikrobiologi

KW - bakteriologi

KW - virologi

KW - mykologi

M3 - Doctoral Thesis (compilation)

SN - 978-91-85897-08-7

T3 - Lund University Faculty of Medicine Doctoral Dissertation Series

PB - Department of Medical Microbiology, Lund University

ER -

Polyomavirus infections in humans

Sammanfattning

Bibliografisk information

Ämnesklassifikation (UKÄ)

FN:s Globala mål

Fingeravtryck

Citera det här