In Vivo and In Vitro Intragenomic Rearrangement of TT Viruses

Abstract

The in vitro replication of the Torque teno virus (TT virus) tth8 full-length genome and particle formation in a Hodgkin's lymphoma-derived cell line after transfection with cloned viral DNA were demonstrated. Analyses of the transcription patterns of tth8 and tth7 TT virus isolates in a number of lymphoma and T-cell leukemia cell lines indicated differential additional splicing events and intragenomic rearrangement generating open reading frames which could not be deducted from the genomic sequence. We also demonstrated the presence of rearranged TT virus genomes in vivo in sera taken from pregnant mothers whose children later developed childhood leukemia, as well as sera from control mothers. Control experiments using religated cloned genomic tth8 DNA mixed with cellular DNA did not result in such subviral molecules. These subviral isolates ranged from 172 bp to full-length TT virus genomes. Possible in vivo selection for specific rearranged molecules was indicated by the presence of one isolate (561 bp) in 11 serum samples. It remains to be clarified whether selected rearranged subviral components resulting from specific TT virus types may contribute to the initiation of disease. These data demonstrate new features of TT viruses suggesting possible similarities to plant viruses of the family Geminiviridae, as well as raise questions about the documented plurality and diversity of anelloviruses.

Expression profile and subcellular localization of Torque teno sus virus proteins

“…Recently, tissue culture systems supporting human TTV replication, with an inefficient propagation, have been reported (Kakkola et al, 2007;Leppik et al, 2007). To date, few studies have focused on molecular virology, transcription and expression strategies of different human TTV genotypes and results are fairly contradictory.…”

“…Moreover, after alternative splicing and alternative translation process, six different proteins from genotype 6 and seven from isolate P/1C1 (genogroup 1) have been described (Müller et al, 2008;Qiu et al, 2005). Additional splicing events and intragenomic rearrangements of TTVs were identified in lymphoma-derived and T-cell leukaemia cell lines (Leppik et al, 2007). TTV genotype 6 ORF1 and ORF2 proteins were localized in the cytoplasm of transfected cells (Qiu et al, 2005).…”

Widely Conserved Recombination Patterns among Single-Stranded DNA Viruses

“…Recombination is known to occur in the parvoviruses (19,43,70), microviruses (66), anelloviruses (40,46), circoviruses (11,26,60), nanoviruses (30), geminivirus DNA-B components, and geminivirus satellite molecules (2,62). Given that most, if not all, of these ssDNA replicons are evolutionarily related to and share many biological features with the geminiviruses (22,31,36), it is of interest to determine whether conserved recombination patterns observed in the geminiviruses (61,81) are evident in these other groups.…”

“…Genome-wide basal recombination rates in ssDNA viruses are probably strongly influenced by the specific characteristics of host DNA polymerases that enable RCR. Interruption of RCR has been implicated directly in geminivirus recombination (40) and is most likely responsible for increased basal recombination rates both within genes transcribed in the opposite direction from that of virion-strand replication (40,71) and at the v-ori (1,9,20,69,74).…”

Antigenic diversity and seroprevalences of Torque teno viruses in children and adults by ORF2-based immunoassays

“…According to transfection studies, TTV transcripts comprise three major species of mRNA (2.8-3.0 , 1.2 and 1.0 kb) Leppik et al, 2007;Qiu et al, 2005), of which the longest, encoding both ORF1 and ORF2 proteins, constitutes approximately 60 % of the total RNA (Qiu et al, 2005). The ORF1 protein product of the largest coding sequence, being the putative capsid protein of TTV, would appear to be a good candidate antigen for serological assays.…”