Human Polyomaviruses in the Cerebrospinal Fluid of Neurological Patients

Abstract

Background: Central nervous system (CNS) infections by human polyomaviruses (HPyVs), with the exception of JC (JCPyV), have been poorly studied.

Methods: In total, 234 cerebrospinal fluid (CSF) samples were collected from patients affected with neurological disorders. DNA was isolated and subjected to quantitative real-time PCR (Q-PCR) for the detection of six HPyVs: JCPyV, BKPyV, Merkel cell PyV (MCPyV), HPyV6, HPyV7, and HPyV9. Where possible, the molecular characterization of the viral strains was carried out by nested PCR and automated sequencing.

Results: JCPyV was detected in 3/234 (1.3%), BKPyV in 15/234 (6.4%), MCPyV in 22/234 (9.4%), and HPyV6 in 1/234 (0.4%) CSF samples. JCPyV was detected at the highest (p < 0.05) mean load (3.7 × 10⁷ copies/mL), followed by BKPyV (1.9 × 10⁶ copies/mL), MCPyV (1.9 × 10⁵ copies/mL), and HPyV6 (3.3 × 10⁴ copies/mL). The noncoding control regions (NCCRs) of the sequenced viral strains were rearranged.

Conclusions: HPyVs other than JCPyV were found in the CSF of patients affected with different neurological diseases, probably as bystanders, rather than etiological agents of the disease. However, the fact that they can be latent in the CNS should be considered, especially in immunosuppressed patients.

Keywords: cerebrospinal fluid; human polyomaviruses; neurological diseases.

Figure 1

Distribution of the viral load of JCPyV, BKPyV, and MCPyV in the CSF. Each bullet point indicates the viral load of a CSF sample, the x indicates the mean viral load, the middle line indicates the median viral load, and the upper and lower lines indicate the maximum and minimum viral load value for each tested virus.

Figure 2

(a) Schematic diagram of the JCPyV and BKPyV VP1 sequences amplified in the CSF. The obtained sequences are compared with genotype 1a for JCPyV [38] and with genotype I for BKPyV [41]. Point mutations are highlighted in bold; (b) schematic diagram, using the typical block representation, of the JCPyV, BKPyV, and MCPyV NCCR sequences amplified in the CSF. The obtained sequences are compared with the archetype CY (accession number AB038249) for JCPyV, with the Dunlop (accession number V01108) or TU strain (accession number LC29411) for BKPyV, and with Type I for MCPyV (accession number EU375803). Point mutations are highlighted in bold.