Impairment of phagosome-lysosome fusion in HIV-1-infected macrophages.
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.
Moorjani
H
H
Division of Infectious Disease, University Medical Center, Stony Brook, New York, USA.
Craddock
B P
BP
Morrison
S A
SA
Steigbigel
R T
RT
D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000502:physiology; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000502:physiology* / Q000821:virology*; D008856:Microscopy, Fluorescence; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000502:physiology* / Q000821:virology
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120