Porcine Circovirus Induces B Lymphocyte Depletion in Pigs with Wasting Disease Syndrome.

Abstract

To disclose the mechanism of cellular injury following porcine circovirus (PCV) infection, 12 pigs were examined by the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) method and immunohistochemistry. Histologically, the lymphoid tissues were characterized by marked apoptosis of lymphocytes, lymphocyte depletion, and macrophages and giant cells containing numerous inclusion bodies with or without apoptotic bodies. Immunohistochemically, there were many lysozyme-positive macrophages in the lymphoid follicles, while the number of CD79a-positive B lymphocytes was scanty. Apoptotic cells, which were proved to be TUNEL positive, revealed CD79a positivity. Although detectable mainly in the cytoplasm of macrophages, PCV antigens were found also in the nuclei of macrophages and apoptotic lymphocytes. Ultrastructurally, the presence of PCV virions was confirmed in apoptotic bodies phagocytosed by macrophages. These findings suggested that lymphocyte depletion with apoptotic death of B lymphocytes was caused by PCV, and that some of the inclusion bodies were phagolysosomes derived from the apoptosis. Thus, PCV may trigger the development of wasting disease syndrome by producing an immunocompromised state in pigs.

Changes in CD4 + , CD8 + , CD4 + CD8 + , and Immunoglobulin M-Positive Peripheral Blood Mononuclear Cells of Postweaning Multisystemic Wasting Syndrome-Affected Pigs and Age-Matched Uninfected Wasted and Healthy Pigs Correlate with Lesions and Porcine Circovirus Type 2 Load in Lymphoid Tissues

“…It was suggested that this decrease could be due to the apoptotic effect that PCV2 infection might have on B cells (23). The results of our analysis of IgM ϩ cell levels showed two different clusters of animals within the PCV2-positive group: pigs with proportions of IgM ϩ cells of Ͻ5% and pigs with proportions of Ͼ5%.…”

“…Some of these changes have been described in other reports (19,20,23), in which the reduction of T cells was associated with a decrease or shift in the CD4 ϩ cell subset (19,20). In those reports, only PCV2-positive or healthy pigs were examined.…”

“…Changes in the proportion of IgM ϩ cells in PBMC of PCV2-infected pigs have been reported (19,20,23). It was suggested that this decrease could be due to the apoptotic effect that PCV2 infection might have on B cells (23).…”

“…In addition, PCV2 antigen in the nuclei of some lymphocyte subsets has been described (23). Recent studies have suggested that PCV2 infects dividing cells, macrophages, and B lymphocytes, inducing apoptosis of the B cells that leads to the depletion of the lymphoid organs (23).…”

“…Moreover, studies of lymphocyte subsets showed that pigs suffering from PMWS had lower proportions of CD4 ϩ and immunoglobulin M-positive (IgM ϩ ) cells in blood than healthy, uninfected pigs did (20). Taken together, these facts have led some to suggest that PCV2 infection might cause immunosuppression (20,23). However, little is known regarding the immunological response of pigs suffering from PMWS and the mechanism by which PCV2 infection might result in the development of PMWS.…”