Polyomavirus infections in humans

University dissertation from Dept of Medical Microbiology, Lund University

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.

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