Volume 17 Issue 1, Pages 45 - 57
Published Online: 5 Dec 2006

Copyright © 2008 John Wiley & Sons, Ltd.

Torque teno virus (TTV): current status
Shigeo Hino 1 *, Hironori Miyata 2
1Department of Virology, Faculty of Medicine, Tottori University, Nishi, Yonago, Japan
2Animal Research Center, University of Occupational and Environmental Health, Japan, Iseigaoka, Yahatanishi,
Kitakyushu, Japan

email: Shigeo Hino (hino@grape.med.tottori-u.ac.jp)

*Correspondence to Shigeo Hino, Department of Virology, Faculty of Medicine, Tottori University, 86 Nishi, Yonago,
683-8503, Japan.

The GenBank/EMBL/DDBJ accession numbers of the partial bovine TTV-NTR sequences reported in this paper
(isolates, Bov7-1, Bov10-1, Bov10-2, Bov24-2, Bov25-3, Bov25-6 and Bov34-2) are AB273626 through AB273632.

Torque teno virus (TTV), currently classified into the family Circoviridae, genus Anellovirus, was first found in a patient
with non-A-E hepatitis. TTV has a single stranded circular DNA of 3.8 kb. TTVs are extraordinarily diverse, spanning
five groups including SANBAN and SEN viruses. Torque teno mini virus (TTMV) with 2.9 kb genome also has wide
variants. Recently, two related 2.2- and 2.6-kb species joined this community. Recombinations between variants are
frequent. This extensive TTV diversity remains unexplained; it is unclear how TTVs could be viable, and why they
require such genetic variation. An unequivocal culture system is still not available. TTVs are ubiquitous in > 90% of
adults worldwide but no human pathogenicity of TTV has been fully established. Epidemiological surveys need to
specify the variants being studied and clinical targets, and must calibrate the sensitivity of the assay used. Potentially
interesting observations include a higher viral load in patients with severe idiopathic inflammatory myopathies, cancer
and lupus. Active replication was also found in infants with acute respiratory diseases. TTV/TTMV-related viruses were
found in chimpanzees, apes, African monkeys and tupaias, and also in chickens, pigs, cows, sheep and dogs.
Experimentally, rhesus monkeys were persistently infected by TTV, but only 1/53 chimpanzees. TTV transcribes three
species of mRNAs, 3.0-, 1.2- and 1.0-kb in the ratio of 60:5:35. Recently, at least three mRNAs were shown in chicken
anaemia virus. The genomic region -154/-76 contains a critical promoter. TTV seems to have at least three proteins;
however, the definite functions of these proteins await further research work. Copyright © 2006 John Wiley & Sons, Ltd.
Received: 20 July 2006; Revised: 6 October 2006; Accepted: 31 October 2006

Currently applied indicator organism systems, such as coliforms, are not fully protective of public health from enteric
viruses in water sources. Waterborne disease outbreaks have occurred in systems that tested negative for coliforms,
and positive coliform results do not necessarily correlate with viral risk.

It is widely recognized that bacterial indicators do not co-occur exclusively with infectious viruses, nor do they respond
in the same manner to environmental or engineered stressors. Thus, a more appropriate indicator of health risks from
infectious enteric viruses is needed.Presentation of the hypothesisTorque teno virus is a small, non-enveloped DNA
virus that likely exhibits similar transport characteristics to pathogenic enteric viruses.

Torque teno virus is unique among enteric viral pathogens in that it appears to be ubiquitous in humans, elicits
seemingly innocuous infections, and does not exhibit seasonal fluctuations or epidemic spikes. Torque teno virus is
transmitted primarily via the fecal-oral route and can be assayed using rapid molecular techniques.

We hypothesize that Torque teno virus is a more appropriate indicator of viral pathogens in drinking waters than
currently used indicator systems based solely on bacteria.Testing the hypothesisTo test the hypothesis, a multi-phased
research approach is needed. First, a reliable Torque teno virus assay must be developed.

A rapid, sensitive, and specific PCR method using established nested primer sets would be most appropriate for routine
monitoring of waters. Because PCR detects both infectious and inactivated virus, an in vitro method to assess infectivity
also is needed.

The density and occurrence of Torque teno virus in feces, wastewater, and source waters must be established to
define spatial and temporal stability of this potential indicator. Finally, Torque teno virus behavior through drinking
water treatment plants must be determined with co-assessment of traditional indicators and enteric viral pathogens to
assess whether correlations exist.

Implications of the hypothesisIf substantiated, Torque teno virus could provide a completely new, reliable, and efficient
indicator system for viral pathogen risk. This indicator would have broad application to drinking water utilities,
watershed managers, and protection agencies and would provide a better means to assess viral risk and protect public

Author: Jennifer S Griffin, Jeanine D Plummer and Sharon C Long
Credits/Source: Virology Journal 2008, 5:112