Torque teno virus microRNA detection in cerebrospinal fluids of patients with neurological pathologies

Abstract

Background: Torque teno virus (TTV) is a widespread anellovirus that establishes persistent infections in humans and represents the most abundant component of the human virome. TTV encodes microRNAs (miRNA) which are found both in viremic and not viremic subjects being potentially ideal tools for the virus to evade the immune system response and to maintain chronic infection in the host.

Objective: To investigate TTV-DNA loads and TTV-miRNAs expression in cerebrospinal fluids (CSF) from subjects under analysis for the assessment of neurological diseases.

Study design: Detection of TTV-DNA and TTV-miRNAs (e. g. miRNA t1a, t3b, and tth8) were carried out from CSF samples of 93 subjects with neurological diseases by using universal real-time PCR, real-time RT-PCR, and next-generation sequencing (NGS) analyses.

Results: TTV-DNA was detected in 11 of 93 (12 %) CSFs with a mean TTV load of 155 copies/mL. Conversely, 29 CSF samples (31 %) were positive for at least one TTV-miRNA, while 15 (16 %) CSFs contained all the TTV-miRNAs examined. Overall, TTV-miRNA tth8 was detected in 62 % of samples, followed by TTV miRNA t3b (56 %), and t1a (29 %). Interestingly, TTV-miRNAs were found in CSF samples that were negative for the presence of TTV-DNA. Next-generation sequencing analysis carried out from 4 TTV-DNA negative CSF samples detected reads mapped in TTV-miRNA sequences region.

Conclusions: These results shed novel light on the relationship between TTV and the central nervous system and make compelling furthered studies for investigating the potential role of TTV-miRNAs in neurological disorders.

Keywords: Anelloviridae; Central nervous system; Cerebrospinal fluid; MicroRNA expression; Torque teno virus.