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 st udy HIV-1 replication in freshly HIV-1-infected peripheral blood monon uclear cells (PBMC) incubated with whole azide-killed C neoformans. Me thods: Human PBMC or peripheral blood lymphocytes were infected with l ymphocytotropic HIV-1 and incubated with azide-killed encapsulated or non-encapsulated C neoformans for 10 days. Viral replication was follo wed by HIV-1 p24 enzyme-linked immunosorbent assay and median tissue c ulture infective dose determination. Tumour necrosis factor (TNF) rele ase by PBMC, induced by C neoformans, was measured. Anti-TNF monoclona l antibodies or pentoxifylline were used to inhibit TNF bioactivity. R esults: Both encapsulated and non-encapsulated C neoformans enhanced H IV-1 replication in PBMC but not in peripheral blood lymphocytes. C ne oformans induced TNF release by PBMC. Inhibition of TNF bioactivity di d not block C neoformans-enhanced HIV-1 replication in PBMC. Conclusio ns: C neoformans can enhance HIV-1 replication in T cells only in the presence of monocytic cells. This enhancement is not dependent on enca psulation nor can it be attributed to TNF release.