IMPAIRMENT OF PHAGOSOME-LYSOSOME FUSION IN HIV-1-INFECTED MACROPHAGES

Phagosome-lysosome fusion is critical for intracellular killing of mos t organisms and is inhibited by some viruses, notably influenza. We ex plored the effects of infection in vitro with HIV-1 (IIIB or Ada-M) on phagosome-lysosome fusion in blood monocyte-derived macrophages. Afte r 8 days of infection, fusion was assessed from the fluorescence chang e occurring up to 2 h after labeling the lysosome compartment with acr idine orange and loading of phagosomes with opsonized yeast. Compared with mock-infected control macrophages, the proportion of cells showin g fusion after infection was reduced from a mean of 70% to a mean of 4 7% (p = 0.0001), Inhibition was seen with heat-killed HLV-1 IIIB but n ot virus-free filtrate. It was mimicked by recombinant gp120 and block ed by soluble CD4 or antibody to CD4 but not by a neutralizing antibod y to the V3 loop of gp120. The inhibitory effect was seen 8 days after the original, transient exposure to gp120. These results suggest that a lasting abnormality of phagosome-lysosome fusion results from inter action between gp120 and CD4, contributing, perhaps, to the increased susceptibility to opportunistic infections of people infected with HIV .