African swine fever: a disease characterized by apoptosis

The cell tropism, organ distribution and resultant pathology of African swine fever were compared in domestic pigs infected with lethal (Malawi) and sublethal (Malta) isolates of African swine fever virus (ASFV). After infections with both isolates, ASFV was predominantly localized in cells of the mononuclear phagocytic system and was not observed in endothelial cells in lymphoid tissue. More severe tissue destruction and cell depletion, associated with high levels of infected macrophages, were seen in lymphoid tissues from domestic pigs infected with the virulent Malawi isolate compared to the less virulent Malta isolate of ASFV. The abundant lymphocyte death was caused by apoptosis and not necrosis. In the spleen, as early as 3 days post-infection (p.i.), many lymphocytes in the B and T cell areas of the white and red pulp were apoptotic. Apoptosis in the T cells of the periarteriolar lymphoid sheaths in the spleen, however, occurred later, at 5-7 days p.i. In lymph nodes apoptosis was observed in T lymphocytes as early as 4 days p.i. and extended to B lymphocytes in the follicles later in infection. In pigs recovered from infection with the sublethal Malta isolate, virus was found to persist in lymph nodes and tonsils for up to 48 days p.i. and was located in cells, surrounded by apoptotic lymphocytes, in the paracortex of lymph nodes up to 32 days p.i. Taken together, these observations suggest that apoptosis of uninfected lymphocytes was induced by cytokines or apoptotic mediators released from ASFV infected macrophages.