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


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.

Download full-text


Available from: Gabriel Gras, Feb 20, 2014
  • Source
    • "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"
    [Show abstract] [Hide abstract]
    ABSTRACT: The complex interactions between genetic machinery of HIV-1 and host immune cells mediate dynamic adaptive responses leading to Autoimmune Deficiency Syndrome. These interactions are captured as Biological Regulatory Network (BRN) which acts to maintain the viability of host cell machinery through feedback control mechanism which is a characteristic of complex adaptive systems. In this study, the BRN of immune response against HIV-1 infection is modeled to investigate the role of NF-κB and TNF-α in disease transmission using qualitative (discrete) and hybrid modeling formalisms. Qualitative and Hybrid modeling approaches are used to model the BRN for the dynamic analysis. The qualitative model is based on the logical parameters while the hybrid model is based on the time delay parameters. The qualitative model gives useful insights about the physiological condition observed as the homeostasis of all the entities of the BRN as well as pathophysiological behaviors representing high expression levels of NF-κB, TNF-α and HIV. Since the qualitative model is time abstracted, so a hybrid model is developed to analyze the behavior of the BRN by associating activation and inhibition time delays with each entity. HyTech tool synthesizes time delay constraints for the existence of homeostasis. Hybrid model reveals various viability constraints that characterize the conditional existence of cyclic states (homeostasis). The resultant relations suggest larger cycle period of HIV-1 than the cycle periods of the other two entities (NF-κB and TNF-α) to maintain a homeostatic expressions of these entities.
    Preview · Article · Dec 2016
  • Source
    • "Antigen-presenting cells (APCs) are critical for both innate and adaptive immunity. Professional APCs such as macrophages play an integral role in the immune pathogenesis of the human immunodeficiency virus type 1 (HIV-1) [1]. HIV-1 is a member of the lentivirus family and is the etiologic agent of acquired immunodeficiency syndrome (AIDS). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Macrophages act as reservoirs of human immunodeficiency virus type 1 (HIV-1) and play an important role in its transmission to other cells. HIV-1 Vpr is a multi-functional protein involved in HIV-1 replication and pathogenesis; however, its exact role in HIV-1-infected human macrophages remains poorly understood. In this study, we used a microarray approach to explore the effects of HIV-1 Vpr on the transcriptional profile of human monocyte-derived macrophages (MDMs). More than 500 genes, mainly those involved in the innate immune response, the type I interferon pathway, cytokine production, and signal transduction, were differentially regulated (fold change >2.0) after infection with a recombinant adenovirus expressing HIV-1 Vpr protein. The differential expression profiles of select interferon-stimulated genes (ISGs) and genes involved in the innate immune response, including STAT1, IRF7, MX1, MX2, ISG15, ISG20, IFIT1, IFIT2, IFIT3, IFI27, IFI44L, APOBEC3A, DDX58 (RIG-I), TNFSF10 (TRAIL), and RSAD2 (viperin) were confirmed by real-time quantitative PCR and were consistent with the microarray data. In addition, at the post-translational level, HIV-1 Vpr induced the phosphorylation of STAT1 at tyrosine 701 in human MDMs. These results demonstrate that HIV-1 Vpr leads to the induction of ISGs and expand the current understanding of the function of Vpr and its role in HIV-1 immune pathogenesis.
    Full-text · Article · Aug 2014 · PLoS ONE
  • Source
    • "Of these, Nef, Tat, Vpr, and Vpu have been detected in soluble forms in sera of HIV-1-infected patients. These are likely to be released by infected/apoptotic cell, enter into macrophages, and then modulate both cellular machinery and viral transcription (Herbein et al. 2010). It is well established that Nef, a 27-kDa protein, downregulates cell surface expression of CD4, CD28, and MHC class I (Lundquist et al. 2002; Yang et al. 2002), thus exerting a key role in HIV pathogenesis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The spread of the human immunodeficiency virus (HIV) has evolved in an alarming manner in terms of human mortality and morbidity, and thus development of an effective and affordable vaccine is a priority to fight this viral disease. As candidate vaccines assessed in clinical trials have shown limited efficacies, efforts to test new candidates capable of inducing strong and neutralizing humoral and cellular responses are underway. This chapter presents a general overview of vaccine candidates produced in plant systems, focusing on the most advanced and promising approaches. This group of candidates comprise strategies targeting structural (Env, Gag) and early non-structural HIV-1 proteins (Rev, Tat, and Nef), which have been expressed in plant tissues using a variety of expression approaches. A number of plant-based vaccines are in preclinical evaluation trials with promising results in terms of immunogenicity.
    Full-text · Chapter · Jun 2014
Show more