A Histopathologic, Immunohistochemical, and Ultrastructural Study of the Intestine in Pigs Inoculated with Classical Swine Fever Virus

Abstract

The aim of this study was to report on the lesions occurring in the intestine during experimental classical swine fever (CSF) and to clarify the nature of infected cells and the distribution of viral antigen. Thirty-two pigs were inoculated with the virulent CSF virus (CSFV) isolate Alfort 187 and slaughtered from 2 to 15 postinoculation days; four animals of similar background served as a control group. Immunohistochemistry, electron microscopy, and the transferase-mediated deoxyuridine triphosphate nick-end labeling method were used to detect viral antigens and apoptosis. The results showed progressive lymphoid depletion and mucosal necrosis. The lymphoid depletion could have been caused by apoptosis of lymphocytes but could not be directly attributed to the effect of CSFV on these cells. Vascular changes, pathogenic bacteria, and viral infection of epithelial cells were ruled out as causes of necrotic lesions. However, large virally infected monocytes-macrophages with ultrastructural changes indicative of activation were observed in the intestine. This suggests that monocytes-macrophages play an important role in the pathogenesis of intestinal lesions. An understanding of the function of these cells will require additional study.

Lymphocyte Apoptosis and Thrombocytopenia in Spleen during Classical Swine Fever: Role of Macrophages and Cytokines

“…Although other studies attribute lymphoid depletion to necrosis, 31,32 recent research has shown that lymphocyte death in CSF is due to apoptosis. 6,41,42,47 The results obtained in this study suggest that the direct virus action on lymphocytes, described in previous studies, 6,32 is not responsible per se for the massive lymphoid depletion in the spleen, but rather, that it plays a secondary role; infection of lymphocytes is certainly observed, but it occurs following the death of these cells. The small number of infected lymphocytes does not tally with the considerable lymphoid depletion exhibited by affected animals, but this depletion does coincide with the numeric increase and secretory activation in m-Møs.…”

“…8 Attention is also drawn to the procoagulant activity of both TNF-␣ and IL-1 and, to a lesser extent, IL-6, 16,46 as well as to the involvement of TNF-␣, together with tissue damage, in the activation of the extrinsic coagulation pathway. 52 Numerous studies have shown that the m-Mø is the prime target cell of classical swine fever (CSF) or hog cholera virus, 21,41,42,47 although lymphocyte infection is also reported in later stages of the disease. 21,47,49 The pathogenic mechanisms involved in the thrombocytopenia and lymphoid depletion observed in CSF remain unclear.…”

“…19,47 Recent research suggests that changes in the function of m-Møs, prompted by infection, alter the secretory properties of these cells; this alteration, coupled with their mobility, may be a decisive factor in the pathogenesis of the disease. 21,41,42 CSF thus affords a useful animal model for biomedical research into the pathogenesis of human virus infections prompting immunosuppression and hemorrhage. Moreover, given its anatomic and physiologic characteristics, the pig is seen as a likely source of organs for xenotransplantation; therefore, more detailed knowledge is required regarding its immune system and the potential consequences of the transmission of pathogens to humans treated with living pig tissues.…”

Expression of E2 (Gp 55) Glycoprotein of Classical Swine Fever Virus in Lymphoid Tissue and Brain of Experimentally Infected Piglets with Different Immunological Status

“…CSF has severe consequences on animal welfare, livestock production, trade and national economy [4]. During CSFV infection immunosupression refl ected in depletion of lymphocytes in lymphoid organs occurs, while severe lymphopenia is present [5][6][7][8][9][10]. Lymphocytes, monocytes, immature granulocytes as well as endothelial cells, have been recognized to be infected with CSFV, consequently leading to morphological changes in various tissues [11].…”

Classical Swine Fever Virus Can Remain Virulent after Specific Elimination of the Interferon Regulatory Factor 3-Degrading Function of N pro

“…Chronic CSFV infections can last up to 100 days (51). N pro might allow the virus to persist in a particular cell type or organ, for example, in vascular endothelial cells (6), lymph nodes, spleen, and intestine, in particular the gut-associated lymphoid tissue (10,42). It is also possible that N pro is important for establishing persistent infections in offspring of animals infected during pregnancy.…”