Macrophage signaling in HIV-1 infection.
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.
Herbein
Georges
G
Department of Virology, UPRES 4266 Pathogens and Inflammation, IFR 133 INSERM, University of Franche-Comté, CHU Besançon, F-25030 Besançon, France. georges.herbein@univ-fcomte.fr
Gras
Gabriel
G
Khan
Kashif Aziz
KA
Abbas
Wasim
W
D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D015398:Signal Transduction; D037521:Virulence Factors / Q000276:immunology / Q000502:physiology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000502:physiology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000502:physiology; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000276:immunology / Q000502:physiology
D015699:HIV Envelope Protein gp120; D037521:Virulence Factors; C514793:gp120 protein, Human immunodeficiency virus 1; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1