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Published on: June 11, 2011
Impaired phagolysosomal fusion of peripheral blood monocytes from HIV-infected subjects
1Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.
Abstract:
We evaluated phagolysosomal fusion in peripheral blood monocytes from 20 HIV-infected individuals and 40 normal controls, using a fluorescence assay with acridine orange as marker. The percentages of phagolysosomal fusion of monocytes from HIV-infected subjects, after 30 and 60 min of yeast ingestion, (mean +/- standard deviation) 57.2 +/- 17 and 63.2 +/- 18.6, respectively, when compared to normal controls (72.4 +/- 7.8 and 77 +/- 8.1), did not differ significantly. However, there was a direct linear association between the percentages of phagolysosomal fusion and CD4+ lymphocytes (P < 0.001) or CD4/CD8 T-cell ratio (P < 0.01). These results suggest that phagolysosomal dysfunction becomes evident at late stages of HIV infection and progresses as CD4+.T-lymphocyte count and CD4/CD8 T-cell ratio decrease. On the other hand, recombinant gp120 inhibited significantly normal phagolysosomal fusion at concentrations ranging between 1 and 1000 ng/ml. Taking together the results obtained, we can conclude that gp120 could be responsible for monocyte phagolysosomal dysfunction observed in HIV infected patients.
Insights
HIV infection impairs monocyte phagolysosomal fusion, particularly in later stages, correlating with decreased CD4+ T-lymphocyte counts. The viral protein gp120 may cause this dysfunction in infected individuals.
Area of Science:
- Immunology
- Virology
Background:
- Human immunodeficiency virus (HIV) infection is known to affect immune cell function.
- Monocytes play a crucial role in innate immunity, including phagocytosis and pathogen clearance.
Purpose of the Study:
- To investigate phagolysosomal fusion capacity in monocytes from HIV-infected individuals.
- To determine the relationship between phagolysosomal fusion and immune markers (CD4+ lymphocytes, CD4/CD8 ratio).
- To assess the role of the HIV envelope protein gp120 in monocyte phagolysosomal dysfunction.
Main Methods:
- Phagolysosomal fusion was assessed in peripheral blood monocytes using an acridine orange fluorescence assay.
- Monocytes from 20 HIV-infected individuals and 40 healthy controls were analyzed.
- The effect of recombinant gp120 on phagolysosomal fusion in normal monocytes was evaluated.
Main Results:
- Phagolysosomal fusion percentages in HIV-infected individuals did not significantly differ from controls at 30 and 60 minutes.
- A significant positive linear association was observed between phagolysosomal fusion and CD4+ lymphocyte counts (P < 0.001) and CD4/CD8 T-cell ratio (P < 0.01).
- Recombinant gp120 significantly inhibited normal phagolysosomal fusion.
Conclusions:
- Monocyte phagolysosomal dysfunction in HIV infection is associated with advanced disease stages and declining CD4+ T-lymphocyte counts.
- The HIV envelope protein gp120 is implicated as a potential cause of monocyte phagolysosomal dysfunction in HIV-infected patients.

