Article

Macrophage signaling in HIV-1 infection

Department of Virology, UPRES 4266 Pathogens and Inflammation, IFR 133 INSERM, University of Franche-Comté, CHU Besançon, F-25030 Besançon, France.
Retrovirology (Impact Factor: 4.19). 04/2010; 7(1):34. DOI: 10.1186/1742-4690-7-34
Source: PubMed

ABSTRACT

The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection.

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Available from: Gabriel Gras, Feb 20, 2014
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    • "er the macrophages , leading to transformation of both cellu - lar and viral transcriptional machinery . Viral glycoprotein 120 ( GP120 ) is essential for HIV - 1 viral entry by interacting with surface receptors CD4 ( Cluster of differentiation 4 ) and CXCR4 ( CXC chemokine receptor 4 ) or CCR5 co - receptor ( chemokine receptor 5 ) ( Fig . 1 ) ( Herbein et al . 1994 , 2010 ; Melikyan 2008 ) . Another important protein that plays significant role both in innate and adaptive immune response is the transcription factor NF - κB . In the absence of foreign antigen ( s ) NF - κB dimers are retained in the cytoplasm through the inhibitory action of the IκB molecules ( Ghosh and Karin 2002 ) . The pro - inflammat"
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