Torque teno viruses (TTVs) are small, non-enveloped viruses with a circular single-stranded DNA genome, belonging to the family Anelloviridae. These viruses are known to infect several vertebrates including human, non-human primates, dogs, cats, wild species and farm animals such as pigs. Most of the current knowledge of Anelloviruses is based on research done with human TTVs but during the recent years, research on swine viruses has been initiated in several laboratories worldwide.

Viral Properties

Anellovirus virions are icosahedral, non-enveloped, with a diameter of 30 to 32nm. In swine, two species have been identified so far, Torque teno sus virus 1 (TTSuV1) and 2 (TTSuV2) belonging to the Iotatorquevirus genus.

The genome of these viruses is small, about 2.8Kb. TTSuV species are genetically very diverse differing from each other more than 50 per cent. Intraspecies nucleotide variation is up to 30 per cent within TTSuV1 and somewhat lower within TTSuV2 (15 per cent) (1,2). Despite their high genetic divergence, the genomic organisation is similar between both viruses, with a coding region containing three overlapping open reading frames and an untranslated region containing the viral promoter and regulatory sequences necessary for transcription and genome replication. (1,2) Protein sequences contain short regions highly conserved in the replication proteins of circular viruses.

Epidemiology

TTSuVs are transmitted both horizontally and vertically. Nasal and faecal samples can be DNA–positive already in one–week–old piglets (3). While prevalence in these samples increases with the age of animals, faecal excretions of 15–week–old pigs is rather low (15 per cent) and nasal detection at the same age animals is higher (30 per cent for TTSuV1 and 55 per cent for TTSuV2). Vertical transmission also occurs since the viruses have been detected in foetal tissues and blood, semen and colostrum (4,5,6,7). Due to efficient transmission routes, TTSuVs are ubiquitous and distributed worldwide. However, a recent study indicates that certain subtypes are dominant in different geographic regions (8).

Tissues from pigs up to five weeks of age and foetuses can be negative or contain low amounts of virus. Tissues from older animals have been found to contain high amounts of both TTSuVs and highest viral prevalence (3,7). Therefore, it seems that infection with TTSuVs leads to a progressive persistent infection that begins at early stages of life (foetus), with increasing prevalence and viral load in tissues with age. High viral loads in the oldest analysed animals might be indicative of an inefficient immune response against the virus.

Currently, no cell culture system for TTSuV propagation exists. The diagnostic of these infections is mainly based on end-point PCR but lately a semi-quantitative PCR for viral DNA load definition in tissue samples (7) and several quantitative PCR methods from serum have been reported (9,10,11)

Disease Association

TTV infects a relatively high proportion of animals that are apparently healthy (10). Therefore, it seems that TTV infection by itself does not cause immediate disease. However, it is believed that TTSuVs can influence the development of some diseases or even affect their outcome.

Evidence for TTSuV disease association has been lately accumulated, especially with regard to porcine circovirus diseases (PCVDs) (12). Specifically, it has been shown that TTSuV2 prevalence is higher in pigs affected by postweaning multisystemic wasting syndrome (PMWS) than healthy animals. Such difference was not evident with TTSuV1 (13) Additionally, utilising the quantitative PCR technique, it has been shown that TTSuV2 viral loads were significantly higher in PMWS–affected animals than in healthy animals, while TTSuV1 loads were not related with the PCVDs (11). On the contrary, one study concluded that neither species seemed to be potential agents able to aggravate PMWS. However, this study used only 11 PMWS–affected and 11 healthy pigs (10).

On the other hand, gnotobiotic pigs inoculated with a tissue homogenate containing TTSuV1 seven days prior to PCV2 challenge developed PMWS under experimental conditions (14). In addition, a PDNS-like condition has also been reproduced by means of the concomitant inoculation of PRRSV and a PRRSV–negative tissue homogenate containing TTSuV1 (15). Therefore, it seems that TTSuV species are not only genetically distinct but also pathologically.

The likelihood of TTSuV co–infection with PCV2 under field conditions is extremely high, while in most of the cases, such co–infection does not lead to a disease but is subclinical. Therefore, the disease association is possibly not only a matter of co-infection, but of viral load. It may be that some TTSuVs are benefiting the disease status of its host by increased viral release or replication. TTSuV viraemia may be associated with the level of immunocompetence of the animals and, therefore, it could be uncontrolled in PMWS animals that are known to be immunocompromised.

Conclusion

Despite of the recent interest and increasing amount of publications, there are still several issues on TTSuVs to be investigated.

One of the most interesting subjects is the disease association; as already suggested by recent publications it is likely that TTSuVs differ in their virulence depending on the viral species/types. One species/type might be more disease-linked than others and co-infection with other viruses could affect the outcome or progression of some diseases, as already shown in human TTVs.

The limitation in the current research is the lack of various techniques like in-situ hybridisation and immunological tools. Due to the high genetic variability, the viral species/types under investigation should be always characterized allowing their possible associations to biological properties.

Acknowledgements

The author thanks the concession of grants AGL2006- 02778/GAN, TRT2006-00018 and CONSOLIDER-PORCIVIR CSD2006-00007 from the Spanish Government. T. Kekarainen is supported by the Spanish Government, Ramón y Cajal program.

Reference

1. Cortey et al. 2011. Vet Microbiol., 148:125-131
2. Huang et al., 2010. Virology, 396:289-297
3. Sibila et al., 2009. Vet Microbiol., 139:213-218
4. Kekarainen et al., 2007. Theriogenology, 68:966-971
5. Martínez-Guinó et al., 2009. Theriogenology, 71:1390-1395
6. Martínez-Guinó et al., 2010. Theriogenology, 74:277-281
7. Aramouni et al., 2010. Vet Microbiol., 146:350-353
8. Cortey et al., 2011. Proc. 6th ERPD, submitted
9. Gallei et al., 2010. Vet Microbiol., 143:202-212
10. Lee et al., 2010. J Vet Diagn Invest., 22:261-264
11. Aramouni et al., 2010. Proc. IPVS, Vancouver
12. Kekarainen and Segalés 2009. Vet J., 180:163-168
13. Kekarainen et al., 2006. J Gen Virol., 87:833-837
14. Ellis et al., 2008. Am J Vet Res., 69:1608-1614
15. Krakowka et al., 2008. Am J Vet Res., 69:1615-162

Reference

Tuija Kekaraine. 2011. Swine Infecting Torque Teno Sus Viruses. International Symposium on Emerging and Re-Emerging Diseases in Pigs, Barcelona, Spain.

Further Reading

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You can view the Proceedings of the 6th International Symposium on Emerging and Re-Emerging Pig Diseases by clicking here.

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Find out more information on PMWS by clicking here.