The pathogenic role of torque teno sus virus 1 and 2 and their correlations with various viral pathogens and host immunocytes in wasting pigs

- A significant positive correlation was present between the TTSuV2 tissue load and the PCV2 tissue load by in situ hybridization.
- The TTSuV1 tissue load was significantly correlated with B cell hyperplasia.
- The TTSuV2 tissue load was significantly correlated with increased macrophage population.
- TTSuV2 infection was correlated with lymphoid depletion and granulomatous inflammation, even when PCV2 was undetectable.
- The pathogenicity of TTSuV is indicated as potentially opportunistic in wasting pigs.

The pathogenic role of torque teno sus virus (TTSuV) in swine is controversial among different studies. The present study intended to evaluate the potential pathogenicity of TTSuV based on its correlations with the histopathological changes, various common concurrently infected viral pathogens including porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV), as well as changes in the distribution and population of host immunocytes such as B lymphocytes, T lymphocytes, and macrophages by using the superficial inguinal lymph nodes (siLNs) of wasting pigs. A tissue microarray consisting of 270 available siLNs collected from 262 clinically wasting and 8 healthy pigs, respectively, were used for the detection of TTSuV1, TTSuV2, PCV2, PRRSV, and PPV by either in situ hybridization (ISH) or immunohistochemical (IHC) staining, and for the detection of various subsets of immunocytes by IHC staining with monoclonal antibodies to CD3, CD79a, and lysozyme. The slides were then subject to digital scanning followed by a semi-quantitative positive pixel evaluation for further statistical analysis. Although a high prevalence of TTSuV1 and/or TTSuV2 infection was noted in both wasting and healthy pigs, the wasting pigs had a significantly higher intensity in both TTSuV1 and TTSuV2 ISH-positive signals than healthy ones did. In the wasting pigs, a significant positive correlation in the tissue viral load was noted between TTSuV1 and TTSuV2 and between TTSuV2 and PCV2, but not between TTSuV1 and PCV2. Conversely, a significant negative correlation in the tissue viral load was revealed between TTSuV2, but not TTSuV1, and PRRSV. The tissue viral load of TTSuV1 was significantly correlated with B cell hyperplasia, while the tissue viral load of TTSuV2 was significantly correlated with increased macrophage population. The ISH positivity of TTSuV2 was significantly correlated with lymphoid depletion and granulomatous inflammation, which are the characteristic histopathological findings in postweaning multisystemic wasting syndrome-affected pigs. These findings suggest that both TTSuV species may have the potential involving the development of porcine circovirus-associated lymphoid lesions via alternating the host immune system.