Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF.
Macrophages play a major role in HIV-1 persistence. In the present paper, we demonstrate that the absence of apoptosis in HIV-1-infected primary human monocyte-differentiated macrophages (MDM) correlates with an increase in anti-apoptotic (Bcl-2 and Bcl-x(L)) and a decrease in pro-apoptotic (Bax and Bad) proteins. This is associated with macrophage activation as shown by tumor necrosis factor (TNF) production and NF-kappaB activation upon infection. TNF production was shown to be involved in the upregulation of Bcl-2 and Bcl-x(L) because this increase was abolished by an anti-TNF anti-serum or an inhibitor of TNF synthesis. In parallel, inhibition of TNF production induced an increase in the number of apoptotic cells. Furthermore, using an inhibitor of NF-kappaB activation, we demonstrated that TNF-induced upregulation of Bcl-x(L) and Bcl-2 occurs, respectively, through a NF-kappaB-dependent and an NF-kappaB-independent pathway.
Guillemard
Eric
E
Unité de Biologie des Rétrovirus, Institut Pasteur, 75724 Paris Cedex 15, France.
Jacquemot
Catherine
C
Aillet
Fabienne
F
Schmitt
Nathalie
N
Barré-Sinoussi
Françoise
F
Israël
Nicole
N
D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C494819:BAD protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D002352:Carrier Proteins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein