nef-deleted HIV-1 inhibits phagocytosis by monocyte-derived macrophages in vitro but not by peripheral blood monocytes in vivo.
AIDS
; 15(8): 945-55, 2001 May 25.
Article
en En
| MEDLINE
| ID: mdl-11399976
ABSTRACT
OBJECTIVE:
HIV-1 infection impairs a number of macrophage effector functions, but the mechanism is unknown. We studied the role of HIV-1 Nef in modulating phagocytosis by human monocytes and monocyte-derived macrophages (MDM). DESIGN ANDMETHODS:
Using a flow cytometric assay, phagocytosis of Mycobacterium avium complex (MAC) by monocytes in whole blood of Sydney Blood Bank Cohort (SBBC) members infected with a nef-deleted (Delta nef) strain of HIV-1 was compared with that of monocytes from uninfected or wild-type (WT) HIV-infected subjects. The specific impact of Nef on phagocytosis by MDM was determined by either infecting cells in vitro with Delta nef strains of HIV-1 or electroporating Nef into uninfected MDM.RESULTS:
MAC phagocytic capacity of monocytes from SBBC members was equivalent to that of cells from uninfected individuals (P = 0.81); it was greater than that of cells from individuals infected with WT HIV-1 (P < 0.0001), irrespective of CD4 counts and HIV viral load. In contrast, in vitro infection of MDM with either Delta nef or WT strains of HIV-1 resulted in similar levels of HIV replication and equivalent impairment of phagocytosis via Fc gamma and complement receptors. Electroporation of Nef into MDM did not alter phagocytic capacity.CONCLUSIONS:
This study provides evidence demonstrating the complex indirect effect of Nef on phagocytosis by peripheral blood monocytes (infrequently infected with HIV-1) in vivo. Conversely, the fact that MDM infected with either Delta nef or WT HIV-1 in vitro (high multiplicity of infection) show comparably impaired phagocytosis, indicates that HIV-1 infection of macrophages can directly impair function, independent of Nef.
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Banco de datos:
MEDLINE
Asunto principal:
Fagocitosis
/
Monocitos
/
Genes nef
/
Infecciones por VIH
/
VIH-1
/
Macrófagos
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Año:
2001
Tipo del documento:
Article