Torque teno virus (TTV) Infection in Patients with Encephalitis

Abstract

Torque teno virus (TTV) is a ssDNA orphan virus belonging to the Anelloviridae family, but some recent studies suggested its possible involvement in central nervous system (CNS) pathology. We analyzed serum and cerebrospinal fluid samples (CSF) from 109 patients with encephalitis for TTV infection using serological and molecular testing, virus quantitative measurement, and next-generation sequencing-based (NGS) phylogenetic analysis. TTV noncoding region (UTR) and/or open reading frame 1 (ORF-1) sequences were detected in serum of 86 (79%) patients and in nine (8%) patients in CSF. Five of the latter patients were coinfected with various entero- and herpesviruses. Anti-TTV-IgG were detected in 80 (73.4%) sera and in two (1.8%) CSF samples, while anti-TTV-IgM were present in three (2.8%) sera and in none of the CSFs. Phylogenic analysis of CSF-derived TTV ORF-1 sequences revealed the presence of three unique variants in one patient. TTV was quantified in five CSF-serum pairs: in two patients viral loads were similar, and in three serum TTV loads were approximately one log higher. Our results suggest at least an occasional replication of TTV in CNS. However, whether TTV could be the cause of encephalitis requires further studies.

Keywords: TTV; Torque teno virus; encephalitis; neuroinfection.

Figure 1

Phylogenetic analysis of the TTV open reading frame 1 (ORF-1) region amplified from serum and CSF in five patients with encephalitis. Phylogenetic trees were generated using MEGA ver. 10. Patient 1 is marked in green, Patient 2 in yellow, Patient 3 in blue, Patient 4 in red, and Patient 5 in orange. Numbers in brackets indicate the number of reads representing each variant. Serum—□S; CSF—ΔC. Unique variants in CSF from patient 5 are underlined in red.