title: BK polyomavirus with archetypal and rearranged non-coding control regions is present in cerebrospinal fluids from patients with neurological complications.
abstract: BK polyomavirus (BKPyV) has recently been postulated as an emerging opportunistic pathogen of the human central nervous system (CNS), but it is not known whether specific strains are associated with the neurotropic character of BKPyV. The presence of BKPyV large T-antigen DNA was examined in 2406 cerebrospinal fluid (CSF) samples from neurological patients with suspected JC polyomavirus infection. Twenty patients had a large T-antigen DNA-positive specimen. The non-coding control region (NCCR) of the BKPyV strains amplified from CSF from these 20 patients, strains circulating in renal and bone marrow transplant recipients and from healthy pregnant women was sequenced. The archetypal conformation was the most prevalent in all groups and 14 of the neurological patients harboured archetypal strains, while the remaining six patients possessed BKPyV with rearranged NCCR similar to previously reported variants from non-neurological patients. Transfection studies in Vero cells revealed that five of six early and four of six late rearranged promoters of these CSF isolates showed significantly higher activity than the corresponding archetypal promoter. From seven of the neurological patients with BKPyV DNA-positive CSF, paired serum samples were available. Five of them were negative for BKPyV DNA, while serum from the remaining two patients harboured BKPyV strains with archetypal NCCR that differed from those present in their CSF. Our results suggest that NCCR rearrangements are not a hallmark for BKPyV neurotropism and the dissemination of a rearranged NCCR from the blood may not be the origin of BKPyV CNS infection.
authors.affiliation: Network of Biomedical Investigation Centres in Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.|Viral Isolation and Detection Laboratory, Microbiology Diagnostic Service, National Microbiology Centre, Carlos III Health Institute, 28220 Majadahonda, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Bárcena-Panero
authors.affiliation: Network of Biomedical Investigation Centres in Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Viral Isolation and Detection Laboratory, Microbiology Diagnostic Service, National Microbiology Centre, Carlos III Health Institute, 28220 Majadahonda, Madrid, Spain.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Echevarría
authors.affiliation: Department of Medical Genetics, University Hospital of Northern-Norway, N-9038 Tromsø, Norway.
authors.forename: Marijke
authors.initials: M
authors.lastname: Van Ghelue
authors.affiliation: Department of Diagnosis Orientation, National Microbiology Centre, Carlos III Health Institute, 28220 Majadahonda, Madrid, Spain.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fedele
authors.affiliation: Network of Biomedical Investigation Centres in Epidemiology and Public Health (CIBERESP), Barcelona, Spain.|Viral Isolation and Detection Laboratory, Microbiology Diagnostic Service, National Microbiology Centre, Carlos III Health Institute, 28220 Majadahonda, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Royuela
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Nancy
authors.initials: N
authors.lastname: Gerits
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: Ugo
authors.initials: U
authors.lastname: Moens
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001739:BK Virus / Q000235:genetics*; D002675:Child, Preschool; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000150:complications / Q000821:virology*; D027601:Polyomavirus Infections / Q000134:cerebrospinal fluid / Q000150:complications / Q000821:virology*; D011247:Pregnancy; D014412:Tumor Virus Infections / Q000134:cerebrospinal fluid / Q000150:complications / Q000821:virology*; D055815:Young Adult
chemical_list: D004279:DNA, Viral