A wide spectrum of diseases of the liver and biliary tree has been observed in patients with AIDS and contributes significantly to the morbidity and mortility in this population. Similar alterations have been described in rhesus macaques with simian acquired immunodeficiency syndrome (SAIDS) which represents an excellent model of the human disease. Preliminary studies of man and rhesus macaques infected with human or simian immunoideficiency virus (HIV, SIV) identified characteristic necroinflammatory, degenerative, and hyperplastic lesions of the bile ducts, so-called """"""""non-suppurative cholangitis."""""""" It is not clear whether these bile duct alterations are directly or indirectly related to infection by HIV/SIV or to secondary complications of AIDS/SAIDS such as superinfections by other infectious agents. It is our long-term objective to elucidate the cellular and molecular mechanism of bile duct injury in AIDS. Based on our preliminary immunopathologic studies, we postulate that bile duct damage in AIDS/SAIDS is mediated by immunologic mechanisms. To evaluate this hypothesis, the liver of rhesus monkeys (Macac alpha mulatta) will be analyzed by quantitative morphologic methods at predetermined time intervals after experimental infection with two strains of SIV with different pathogenic potentials. SIV and other viruses (cytomegalovirus and Epstein-Barr virus) will be localized in the liver of infected monkeys by immunohistochemical and in situ hybridization methods. Bile duct damage will be quantitated by light and electron microscopic morphometry. HLA class I and class II antigens, IgA, and cytokeratins will be demonstrated in the bile ducts by immunohistochemical methods at the light and ultrastructural levels. The mononuclear cell subpopulations infiltrating the portal tracts around the bile ducts will be enumerated by immunomorphometric methods. These quantitative data will be correlated with the duration and course of experimental SIV infections, the state of the disease, and the immunologic and virologic status of the rhesus macaques with SAIDS. The observations will also be compared with the bile duct disease in patients with AIDS. We hope that these studies will lead to a better understanding of bile duct injury and to a more rational management of liver disease in patients with AIDS.
