Porcine Circovirus Type 2 Pathogenicity Alters Host's Central Tolerance for Propagation.

Porcine circovirus type 2 (PCV2) infections and resulting diseases are a worldwide threat to pig production. PCV2 bears a uniqueness that allows for us to understand more about chronic infections and the immune system in general. The virus can be phylogenetically subdivided into PCV2a to PCV2h genotypes. Although vaccination against PCV2 has been seen to prevent the manifestation of PCV disease, PCV2 still lingers as subclinical infections in all developmental stages of pigs. The "slow and low" tactic gives PCV2 a particular advantage in a host's immune surveillance. Since the inception of the PCV2 associated panzootic, research scientists have been trying to understand the pathogenicity of PCV2. Different research groups found that one genotype group member was more pathogenic than others. We found, in our weaner infection model with in vivo transfection of different recombinant PCV2 genotype group members that these viruses alter T cell maturation in the thymus, including host's central tolerance. Here, we extend these original observations by showing that PCV2 infected cells were also found in proximity within the female and male reproductive organs of stillborn pig fetuses. These PCV2 pools were sufficient in infecting three and half-day-old embryos in sows. Furthermore, the dominant PCV2 group member was more pathogenic in our weaner infection model. PCV2 pre-immunocompetence infection makes PCV2 recognized by central immune tolerance as belonging to the host. This also explains why pathogenicity is not a genetically intrinsic characteristic of PCV2; however, the dominance of any one PCV2 genotype group member leads to a more efficient deletion of the T cells against that specific genotype group member in the thymus.

T-cell reprogramming through targeted CD4-coreceptor and T-cell receptor expression on maturing thymocytes by latent Circoviridae family member porcine circovirus type 2 cell infections in the thymus.

Although porcine circovirus type 2 (PCV2)-associated diseases have been evaluated for known immune evasion strategies, the pathogenicity of these viruses remained concealed for decades. Surprisingly, the same viruses that cause panzootics in livestock are widespread in young, unaffected animals. Recently, evidence has emerged that circovirus-like viruses are also linked to complex diseases in humans, including children. We detected PCV2 genome-carrying cells in fetal pig thymi. To elucidate virus pathogenicity, we developed a new pig infection model by in vivo transfection of recombinant PCV2 and the immunosuppressant cofactor cyclosporine A. Using flow cytometry, immunofluorescence and fluorescence in situ hybridization, we found evidence that PCV2 dictates positive and negative selection of maturing T cells in the thymus. We show for the first time that PCV2-infected cells reside at the corticomedullary junction of the thymus. In diseased animals, we found polyclonal deletion of single positive cells (SPs) that may result from a loss of major histocompatibility complex class-II expression at the corticomedullary junction. The percentage of PCV2 antigen-presenting cells correlated with the degree of viremia and, in turn, the severity of the defect in thymocyte maturation. Moreover, the reversed T-cell receptor/CD4-coreceptor expression dichotomy on thymocytes at the CD4(+)CD8(interm) and CD4SP cell stage is viremia-dependent, resulting in a specific hypo-responsiveness of T-helper cells. We compare our results with the only other better-studied member of Circoviridae, chicken anemia virus. Our data show that PCV2 infection leads to thymocyte selection dysregulation, adding a valuable dimension to our understanding of virus pathogenicity.

T-cell lymphoma in the nasal cavity of a Brown Swiss heifer.

BACKGROUND: Tumours of the upper respiratory tract are relatively common in cattle, but to our knowledge, there have been no reports of lymphoma of the nasal cavity. This case report describes the findings in a 22-month-old Brown Swiss heifer with T-cell lymphoma of the nasal cavity. CASE PRESENTATION: The main clinical findings were lacrimation and swelling of the head above and below the right eye, mild exophthalmos, third eyelid prolapse, purulent ocular discharge and congestion of scleral blood vessels. An endoscope could only be introduced a few centimetres into the right nasal cavity because of an obstructing mass in the nasal passage. Radiographs showed a mass in the right nasal cavity and maxillary sinus. A tentative diagnosis of neoplasia of the right nasal cavity was made and the heifer was euthanased and necropsied. A firm, tan mass measuring 10 by 13 by 15 cm in the right half of the head occupied the entire right nasal cavity. A final diagnosis of high-grade, malignant, small-sized T-cell lymphoma was made based on histological and immunohistochemical evaluation. A distinction between αß T-cell or γδ T-cell lymphoma was not made. CONCLUSIONS: This report on T-cell lymphoma in the nasal cavity of a cow suggests that nasal lymphoma should be included in the list of differential diagnosis of conditions associated with dyspnoea and stertorous breathing in cattle.