Tesis doctoral de Ana Barcena Panero
Human polyomavirus bk (bkpyv) is the aetiological agent of polyomavirus-associated nephropathy (pvan) and of hemorrhagic cystitis (hc) while human polyomavirus jc (jcpyv) is associated with progressive multifocal leukoencephalopathy (pml). However, j cpyv can give rise to pvan and hc and bkpyv has been detected in cerebrospinal fluid samples (csf) from patients with central nervous system disease, including pml. During the period 1998¿2010, 2,406 csf samples from patients with suspected jcpyv inf ection were tested for the presence of bkpyv, jcpyv, and sv40 large t antigen dna by a multiplex pcr assay in the national centre of microbiology in spain. Twenty neurological patients with at least one bkpyv dna-positive csf specimen were identified . considering the proven usefulness of diagnostic tools that are able to detect both bkpyv and jcpyv in the same reaction tube, our study aimed to develop a real-time pcr that can detect and quantify both viruses simultaneously. Due to the scarce nu mber of cases described, bkpyv-associated neurological infection has been very poorly characterized. One of our objectives was to quantify bkpyv in neurological patients for the first time. Another goal was to investigate whether bkpyv-associated neu rological infection is linked to specific neurotropic bkpyv strains, as in the case of jcpyv. firstly, an internally-controlled multiplex real-time pcr was developed and showed to be suitable for the diagnosis of polyomavirus bk and jc infection, pr oviding a sensitive, reproducible and specific quantification of the viral load of both viruses in samples of patients with associated pathologies. The present method was used to quantify bkpyv in the csf of neurological patients for the first time, showing a median of 9 x 103 copies/ml (range 6 x102- 2x 106 copies/ml) and no differences were observed with jcpyv viral load in pml patients. secondly, bkpyv non coding control region (nccr) sequences from the 20 neurological patients were determine d and compared to nccr sequences from bkpyv variants present in renal transplant recipients, bone marrow transplant recipients and healthy pregnant women. The archetypal conformation of bk polyomavirus regulatory region was detected in 14 of the neur ological patients, while the remaining six patients harbored rearranged strains similar to variants previously reported in non-neurological patients. Therefore, rearrangements are not sufficient per se to induce neurotropism. Five out of six early an
Datos académicos de la tesis doctoral «Caracterización de la infección neurológica por poliomavirus bk«
- Título de la tesis: Caracterización de la infección neurológica por poliomavirus bk
- Autor: Ana Barcena Panero
- Universidad: Complutense de Madrid
- Fecha de lectura de la tesis: 08/10/2012
Dirección y tribunal
- Director de la tesis
- Giovanni Fedele
- Tribunal
- Presidente del tribunal: carmen Rodríguez-avial lópez-doriga
- María rosa Ciardi (vocal)
- Juan Francisco Pozo sánchez (vocal)
- Marta Fogea moreno (vocal)