ENHANCEMENT OF HIV-1 REPLICATION IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS BY CRYPTOCOCCUS-NEOFORMANS IS MONOCYTE-DEPENDENT BUT TUMOR NECROSIS FACTOR-INDEPENDENT

Objective: To investigate the possible role of Cryptococcus neoformans in HIV-1 pathogenesis. Design: An in vitro system was developed to study HIV-1 replication in freshly HIV-1-infected peripheral blood mononuclear cells (PBMC) incubated with whole azide-killed C neoformans. Methods: Human PBMC or peripheral blood lymphocytes were infected with lymphocytotropic HIV-1 and incubated with azide-killed encapsulated or non-encapsulated C neoformans for 10 days. Viral replication was followed by HIV-1 p24 enzyme-linked immunosorbent assay and median tissue culture infective dose determination. Tumour necrosis factor (TNF) release by PBMC, induced by C neoformans, was measured. Anti-TNF monoclonal antibodies or pentoxifylline were used to inhibit TNF bioactivity. Results: Both encapsulated and non-encapsulated C neoformans enhanced HIV-1 replication in PBMC but not in peripheral blood lymphocytes. C neoformans induced TNF release by PBMC. Inhibition of TNF bioactivity did not block C neoformans-enhanced HIV-1 replication in PBMC. Conclusions: C neoformans can enhance HIV-1 replication in T cells only in the presence of monocytic cells. This enhancement is not dependent on encapsulation nor can it be attributed to TNF release.