Analysis of the entire genomes of torque teno midi virus variants in chimpanzees: infrequent cross-species infection between humans and chimpanzees

Abstract

Humans are frequently infected with three anelloviruses which have circular DNA genomes of 3.6-3.9 kb [Torque teno virus (TTV)], 2.8-2.9 kb [Torque teno mini virus (TTMV)] and 3.2 kb [a recently discovered anellovirus named Torque teno midi virus (TTMDV)]. Unexpectedly, human TTMDV DNA was not detectable in any of 74 chimpanzees tested, although all but one tested positive for both human TTV and TTMV DNA. Using universal primers for anelloviruses, novel variants of TTMDV that are phylogenetically clearly separate from human TTMDV were identified from chimpanzees, and over the entire genome, three chimpanzee TTMDV variants differed by 17.9-20.3 % from each other and by 40.4-43.6 % from all 18 reported human TTMDVs. A newly developed PCR assay that uses chimpanzee TTMDV-specific primers revealed the high prevalence of chimpanzee TTMDV in chimpanzees (63/74, 85 %) but low prevalence in humans (1/100). While variants of TTV and TTMV from chimpanzees and humans were phylogenetically interspersed, those of TTMDV were monophyletic for each species, with sequence diversity of ,33 and ,20 % within the 18 human and three chimpanzee TTMDV variants, respectively. Maximum within-group divergence values for TTV and TTMV were 51 and 57 %, respectively; both of these values were substantially greater than the maximum divergence among TTMDV variants (44 %), consistent with a later evolutionary emergence of TTMDV. However, substantiation of this hypothesis will require further analysis of genetic diversity using an expanded dataset of TTMDV variants in humans and chimpanzees. Similarly, the underlying mechanism of observed infrequent cross-species infection of TTMDV between humans and chimpanzees deserves further analysis. INTRODUCTIONTorque teno virus (TTV) was first discovered in the serum of a patient with cryptogenic hepatitis following transfusion in 1997 (Nishizawa et al., 1997;Okamoto et al., 1998). In 2000, torque teno mini virus (TTMV) was accidentally identified by PCR using TTV-specific primers that partially matched homologous sequences but generated unexpectedly shorter amplicons . TTV and TTMV are both small, unenveloped spherical viruses with circular single-stranded DNA genomes of 3.6-3.9 and 2.8-2.9 kb, respectively (Miyata et al., 1999;Mushahwar et al., 1999;Okamoto et al., 1998Okamoto et al., , 1999Okamoto et al., , 2000bTakahashi et al., 2000;Peng et al., 2002). The International Committee on Taxonomy of Viruses officially classified TTV and TTMV into the new floating genus Anellovirus (Biagini et al., 2005).Recently, a third group of TTV-like viruses, termed small anellovirus (SAV) types 1 and 2 (SAV-1 and SAV-2) were cloned from plasma samples of individuals at high risk for human immunodeficiency virus (HIV) infection (Jones et al., 2005). Further characterization revealed that these viruses have a circular DNA genome of 3.2 kb, intermediate in size between TTV and TTMV, but with an otherwise similar genomic organization (Ninomiya et al., 3Present address: Department of Gastroenterology, Tohoku University...

Torque Teno Midi Virus/Small Anellovirus in Sera of Healthy, HIV/HCV and HIV Infected Individuals in Lorestan Province, Iran

“…In the gel electrophoresis expected 431 base pair product for SAV2 and 441 bp product for SAV1 ( 4 , 8 ) were observed ( Figure 1 ). Alignment of the seven obtained sequences (GenBank accession numbers: KC352905, KC352906, KC352907, KC352908, KC352909, KC352910, KC352911) revealed a high degree of genetic variability among the TTMDV/SAV DNA (homology ranging from 70% to 93%) with some sequences in the Gen Bank.…”

“…In 2007, Ninomyia et al identified a novel DNA virus with a genomic organization resembling those of TTV and TTMV and designated this new virus as Torque Teno Midi Virus (TTMDV), they also showed that Small Anellovirus (SAV1) and SAV2 were deletion mutants or artifacts generated during the amplification of TTMDV ( 3 ). Therefore, these viruses were named TTMDV/SAV and then TTMDV viruses and were classified as Gammatorquevirus genus (including 15 species: Torque teno midi virus 1 - 15) of the family ( 1 - 4 ).…”

Metagenomic identification of a novel anellovirus in Pacific harbor seal (Phoca vitulina richardsii) lung samples and its detection in samples from multiple years

“…ORF2 encodes 111 amino acids and shares no amino acid sequence identity with proteins in GenBank. ORF2 lacks the motif W-X 7 -H-X 3 -C-X 1 -C-X 5 -H that is conserved among TTVs, TTMVs and TTMDVs (Hijikata et al , 1999; Ninomiya et al , 2007, 2009; Okamoto et al , 2000; Takahashi et al , 2000). ORF3 encodes 204 amino acids, and shares weak amino acid sequence identity (16 %) with ZcAV ORF3 only, indicating that SealAV could be more closely related to ZcAV than to other anelloviruses.…”

A novel species of torque teno mini virus (TTMV) in gingival tissue from chronic periodontitis patients

“…Human anelloviruses were first discovered in 1997 and have been classified into three genera in the family Anelloviridae : TTV, genus Alphatorquevirus ; TTMV, genus Betatorquevirus ; and torque teno midi virus (TTMDV), genus Gammatorquevirus 36 37 . Their genomes consist of small, single-stranded circular DNA, and their capsids have no lipid envelopes.…”