RESUMO
Phagosome-lysosome fusion is critical for intracellular killing of most organisms and is inhibited by some viruses, notably influenza. We explored the effects of infection in vitro with HIV-1 (IIIB or Ada-M) on phagosome-lysosome fusion in blood monocyte-derived macrophages. After 8 days of infection, fusion was assessed from the fluorescence change occurring up to 2 h after labeling the lysosome compartment with acridine orange and loading of phagosomes with opsonized yeast. Compared with mock-infected control macrophages, the proportion of cells showing fusion after infection was reduced from a mean of 70% to a mean of 47% (p = 0.0001). Inhibition was seen with heat-killed HIV-1 IIIB but not virus-free filtrate. It was mimicked by recombinant gp 120 and blocked by soluble CD4 or antibody to CD4 but not by a neutralizing antibody to the V3 loop of gp 120. The inhibitory effect was seen 8 days after the original, transient exposure to gp 120. These results suggest that a lasting abnormality of phagosome-lysosome fusion results from interaction between gp 120 and CD4, contributing, perhaps, to the increased susceptibility to opportunistic infections of people infected with HIV.
