Cryptococcosis with disseminated disease has emerged as a primary cause of opportunistic infections associated with Acquired Immunodeficiency Syndrome (AIDS). Pneumocystis carinii (pneumonia), Cryptococcus neoformans (cryptococcosis), Toxoplasma gondii (toxoplasmosis), Mycobacterium avium-M. intercellular occur as opportunistic infections in 50-70% of AIDS patients. Approximately 10% of AIDS patients have cryptococcosis. Although the yeast can affect any organ, it has a predilection for the central nervous system, where it causes cryptococcal meningoencephalitis. If gone untreated this disease is fatal and is the cause of death in one of five AIDS patients. In the pre-AIDS era both varieties of C. Neoforman (C. neoformans var. neoformans and C. neoformans var. gattii) were isolated from clinical specimens whereas today c. neoformans isolates from AIDS patients are almost invariably of the neoformans variety. There appears to be a selective infection of AIDS patients with the neoformans variety and 99% of these are of the A serotype. The capsular polysaccharide injures certain aspects of the immune system; inhibition of phagocytosis, depletion of complement, and induction of suppressor T-cell networks. In a recent report the capsular polysaccharide was shown to enhance HIV-1 infectivity in H9 cells. It has also been demonstrated that other cell envelope antigens may play a role in the enhancement of HIV-1 replication in T-cells. The research from this laboratory emphasizes the characterization of C. neoformans at the molecular level, capsule structure and sequence, other cell envelope antigens, cell wall glucans, and epitope structure. Exact chemical sequences present in glucuronoxylomannan (GXM) of C. neoformans are being determined by using advanced methods in nuclear magnetic resonance spectroscopy. Epitope specificity of monoclonal antibodies, Factor sera, and polyclonal rabbit sera-fractionated by tandem-column affinity chromatography with purified GXMs serving as the immobilized ligand-are being determined. The isolated, purified, and characterized antigens are useful in the study of the mechanisms by which C. neoformans effects the immune system in normal or immunocompromised hosts (AIDS), in culture, and in animal models.
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