Pathogenesis and genetic diversity of rodent Torque teno virus

Abstract

Torque teno virus (TTV) is a single stranded circular DNA virus and, despite its widespread nature in the human population, its pathogenesis is still unknown. Factors complicating TTV research include its huge genetic diversity, difficulties identifying an uninfected control population, the lack of a small animal model and lack of a good cell culture system for viral propagation. Recently we have identified a TTV homologue (RoTTV) in wild rodents. RoTTV was frequently observed in wood mice and field voles. RoTTV infections were also found in bank voles but not in Mus musculus populations. Analysis of complete genome sequencing shows that several genetic variants are found in wild rodent population with two distinct species containing several diverse genotypes. Furthermore, multiple variants were present in single individuals, consistent with infection patterns seen in humans. RoTTV transcripts in infected wild wood mice have also been detected and fully sequenced. Predicted protein coding regions from these transcripts have been expressed in cell culture and show the different expression patterns. Using cloned genomic DNA it has also been possible to observe the transcription from the virus in vitro and it was shown RoTTV viral titer in the supernatant of culture fluid increased. In addition, RoTTV propagation was observed by using the supernatant of culture fluid. Using cloned genomic DNA and the culture supernatant, an in vivo model system in naïve laboratory wood mice was developed

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