High frequency of Human Polyomavirus 6 DNA in the cerebrospinal fluid of patients with neurological diseases

Background: The family Polyomaviridae comprises thirteen human viruses that have been detected in various specimen types, mainly urine, skin and blood. Among all of them, only JC Polyomavirus (JCPyV), and sporadically BK polyomavirus (BKPyV) genomes have been detected in the Cerebrospinal Fluid (CSF). More recently, the unexpected finding of Human Polyomavirus 6 (HPyV6) DNA in the CSF from an HIV positive patient with leukoencephalopathy was reported. JCPyV being a recognized cause of Progressive Multifocal Leukoencephalopathy (PML) in immunodeficient subjects provides a precedent for polyomavirus causing neurological symptoms, but alternative explanations should also be considered. The objectives of the study were to explore the prevalence of the newly discovered HPyV6, Human Polyomavirus 7 (HPyV7) and Human Polyomavirus 9 (HPyV9) in neurological dis- eases, in comparison with those of JCV. Methods: CSF have been collected from 51 HIV-positive patients affected with HIV-related leukoencephalopathies and 191 HIV-negative patients affected with other neurological diseases (OND), such as meningitis, encephalitis, and encephalomyelitis. DNA was isolated and real-time PCR assays for JCV, HPyV6, HPyV7 and HPyV9 were conducted. Results: JCV genome was detected in the CSF of 16/51 (31.4%)HIV-related leukoencephalopathies patients, HPyV6 genome in the CSF of 2/51 (3.9%) HIV-related leukoencephalopathies patients and in 37/191 (19.4%) HIV-negative patients with OND. HPyV7 and HPyV9 genomes were not amplified in any clinical specimens. Conclusions: HPyV6 genome was found in a high percent- age of the CSF of the OND patients, whereas HPyV7 and HPyV9 genomes were not detected. HPyV6 has not been previously associated with any disease, and it is nonetheless possible that the HPyV6 sequences originated from the skin during CSF collection. Whether HPyV6 detection in CSF is associated with patients’ neurological disease, is indicative of contamination with skin microbiota, or reflects increased blood-brain permeability is unknown. Demonstrating a causative role will require further studies.