Analysis of the entire genomes of fifteen torque teno midi virus variants classifiable into a third group of genus Anellovirus

Jichi Medical University, Totigi, Tochigi, Japan
Archives of Virology (Impact Factor: 2.39). 02/2007; 152(11):1961-75. DOI: 10.1007/s00705-007-1046-6
Source: PubMed


Recently, we identified a novel human virus with a circular DNA genome of 3.2 kb, tentatively designated as torque teno midi virus (TTMDV), with a genomic organization resembling those of torque teno virus (TTV) of 3.8-3.9 kb and torque teno mini virus (TTMV) of 2.8-2.9 kb. To investigate the extent of genomic variability of TTMDV genomes, the full-length sequence was determined for 15 TTMDV isolates obtained from viremic individuals in Japan. The 15 TTMDV isolates comprised 3175-3230 bases and shared 67.0-90.3% identities with each other, and were only 68.4-73.0% identical to the 3 reported TTMDV isolates over the entire genome. TTMDV possessed a genomic organization with four open reading frames (ORF1-ORF4) with characteristic sequence motifs and stem and loop structures with high GC content, similar to TTV and TTMV. The total of 18 TTMDV genomes differed by up to 60.7% from each other in the amino acid sequence of ORF1 (658-677 amino acids), but segregated phylogenetically into the same cluster, which was distantly related to the TTVs and TTMVs. These results indicate that TTMDV with a circular DNA genome of 3.2 kb, has an extremely high degree of genomic variability, and is classifiable into a third group in the genus Anellovirus.

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    • "To determine whether or not divergent sequences could be identified using targeted sequence capture, we tested ViroCap on samples containing anelloviruses, a highly divergent group of ssDNA viruses that have a common genome structure but may have up to 30%–50% nucleotide sequence diversity among separate species (Ninomiya et al. 2007; de Villiers et al. 2011). We selected anellovirus-positive samples that we had previously characterized using multistrand displacement amplification followed by highthroughput sequencing. "
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    ABSTRACT: Metagenomic shotgun sequencing (MSS) is an important tool for characterizing viral populations. It is culture-independent, requires no a priori knowledge of the viruses in the sample, and may provide useful genomic information. However, MSS can lack sensitivity and may yield insufficient data for detailed analysis. We have created a targeted sequence capture panel, ViroCap, designed to enrich nucleic acid from DNA and RNA viruses from 34 families that infect vertebrate hosts. A computational approach condensed nearly 1 billion base pair (bp) of viral reference sequence into less than 200 million bp of unique, representative sequence suitable for targeted sequence capture. We compared the effectiveness of detecting viruses in standard MSS versus MSS following targeted sequence capture. First, we analyzed two sets of samples, one derived from samples submitted to a diagnostic virology laboratory and one derived from samples collected in a study of fever in children. We detected 14 and 18 viruses in the two sets, comprising 19 genera from 10 families, with dramatic enhancement of genome representation following capture enrichment. The median fold-increases in percent viral reads post-capture were 674 and 296. Median breadth of coverage increased from 2.1% to 83.2% post-capture in the first set and from 2.0% to 75.6% in the second set. Next, we analyzed samples containing a set of diverse anellovirus sequences and demonstrated that ViroCap could be used to detect viral sequences with up to 58% variation from the references used to select capture probes. ViroCap substantially enhances MSS for a comprehensive set of viruses and has utility for research and clinical applications.
    Full-text · Article · Sep 2015 · Genome Research
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    • "Since that initial discovery, a large and diverse population of human anelloviruses has been characterized. There are currently five genogroups of TTV, as well as two separate viral genera containing viruses with similarities in genomic organizations but smaller genome size and a virtual absence in identifiable sequence homology throughout large parts of the genome designated torque teno midi virus (TTMDV) (Jones et al., 2005; Ninomiya et al., 2007a, b) and torque teno mini virus (TTMV) (Takahashi et al., 2000). In addition, there has been a large number of anellovirus species reported in wild and domesticated animals, including pigs, wild boar, camels, cats, dogs, pine martens, badgers, sea lions and a number of non-human primates (Abe et al., 2000; Al-Moslih et al., 2007; Martínez et al., 2006; Ng et al., 2009b; Okamoto et al., 2001b, 2002; Romeo et al., 2000; Thom et al., 2003; van den Brand et al., 2012; Verschoor et al., 1999). "
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    ABSTRACT: Anelloviruses are a family of small single stranded circular DNA viruses with a vast genetic diversity. Human infections with the prototype anellovirus, torque teno virus (TTV), are ubiquitous and related viruses have been described in a number of other mammalian hosts. Despite over 15 years of investigation, however, there is still little known about the pathogenesis and possible disease associations of anellovirus infections, arising in part due to the lack of a robust cell culture system for viral replication or tractable small animal model. We report the identification of diverse anelloviruses in several species of wild rodents. The viruses are highly prevalent in wood mice (Apodemus sylvaticus) and field voles (Microtus agrestis), detectable at a low frequency in bank voles (Myodes glareolus) but absent from house mice (Mus musculus). The viruses identified have a genomic organisation consistent with other anelloviruses but form two clear phylogenetic groups that are as distinct from each other as from defined genera.
    Full-text · Article · Apr 2014 · Journal of General Virology
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    • "kb for TTV, 3.2 kb for TTMDV, and 2.8–2.9 kb for TTMV. A characteristic feature of anelloviruses is the extreme diversity found both within and between anellovirus species; they can exhibit as much as 33%–50% divergence at the nucleotide level [3], [13], [14], [15], [16], [17], [18], [19], [20]. Despite the nucleotide sequence diversity, anelloviruses share conserved genomic organization, transcriptional profiles, a non-coding GC rich region, and sequence motifs resulting in shared virion structure and gene functions [3], [21], [22], [23], [24], [25], [26], [27]. "
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    ABSTRACT: The Anelloviridae family consists of non-enveloped, circular, single-stranded DNA viruses. Three genera of anellovirus are known to infect humans, named TTV, TTMDV, and TTMV. Although anelloviruses were initially thought to cause non-A-G viral hepatitis, continued research has shown no definitive associations between anellovirus and human disease to date. Using high-throughput sequencing, we investigated the association between anelloviruses and fever in pediatric patients 2-36 months of age. We determined that although anelloviruses were present in a large number of specimens from both febrile and afebrile patients, they were more prevalent in the plasma and nasopharyngeal (NP) specimens of febrile patients compared to afebrile controls. Using PCR to detect each of the three species of anellovirus that infect humans, we found that anellovirus species TTV and TTMDV were more prevalent in the plasma and NP specimens of febrile patients compared to afebrile controls. This was not the case for species TTMV which was found in similar percentages of febrile and afebrile patient specimens. Analysis of patient age showed that the percentage of plasma and NP specimens containing anellovirus increased with age until patients were 19-24 months of age, after which the percentage of anellovirus positive patient specimens dropped. This trend was striking for TTV and TTMDV and very modest for TTMV in both plasma and NP specimens. Finally, as the temperature of febrile patients increased, so too did the frequency of TTV and TTMDV detection. Again, TTMV was equally present in both febrile and afebrile patient specimens. Taken together these data indicate that the human anellovirus species TTV and TTMDV are associated with fever in children, while the highly related human anellovirus TTMV has no association with fever.
    Full-text · Article · Nov 2012 · PLoS ONE
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