Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF.

Abstract

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.

• Authors: Eric Guillemard, Catherine Jacquemot, Fabienne Aillet, Nathalie Schmitt, Françoise Barré-Sinoussi, Nicole Israël
• Journal: Virology (Virology) Vol. 329 Issue 2 Pg. 371-80 (Nov 24 2004) ISSN: 0042-6822 [Print] United States
• PMID: 15518816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAD protein, human
• BAX protein, human
• BCL2L1 protein, human
• Carrier Proteins
• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Tumor Necrosis Factor-alpha
• bcl-2-Associated X Protein
• bcl-Associated Death Protein
• bcl-X Protein

Topics

• Apoptosis
• Carrier Proteins (metabolism)
• Cell Death
• Cells, Cultured
• HIV-1 (physiology)
• Humans
• Macrophage Activation
• Macrophages (metabolism, virology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Time Factors
• Tumor Necrosis Factor-alpha (antagonists & inhibitors, biosynthesis, physiology)
• Up-Regulation
• bcl-2-Associated X Protein
• bcl-Associated Death Protein
• bcl-X Protein