Apoptosis in rabbit haemorrhagic disease

Rabbit haemorrhagic disease virus (RHDV) causes an acute hepatitis and disseminated intravascular coagulation. Six rabbits were inoculated experimentally with RHDV to investigate any potential relationship between infection and apoptosis in the liver. Two rabbits were killed at 12 h post-inoculation (PI) and two at 24 h PI. The remaining two rabbits died at 30 h and 31 h PI. Immunohistochemical labelling for RHDV antigen-positive cells, TUNEL assay for apoptotic cells, and DNA analysis were performed on samples of liver. The four rabbits that died or were killed 24-31 h PI had acute hepatitis with infiltration of heterophils and necrotic hepatocytes. RHDV antigen-positive cells and apoptotic cells appeared in the centriacinar areas at 12 h PI; subsequently they spread to periacinar areas and increased in number, but the viral antigen-positive cells outnumbered apoptotic cells. At 24-31 h PI, few apoptotic cells were recognized in the areas infiltrated with lymphocytes and heterophils. The results suggested an association between RHDV infection and apoptosis of hepatocytes.