Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview

• Published in: Cell death & disease Vol. 6; no. 8; p. e1846
• Main Authors: Nardacci, R, Perfettini, J-L, Grieco, L, Thieffry, D, Kroemer, G, Piacentini, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.08.2015; Springer Nature B.V; Nature Publishing Group
• Subjects: 13; 13/2; 13/51; 13/89; 631/250/255/1901; 631/80/82/23; 631/80/86; 692/700/565; 82; 96; 96/35; 96/63; Antibodies; Apoptosis - genetics; Biochemistry; Biomedical and Life Sciences; Bystander Effect - genetics; CD4 Antigens - genetics; CD4 Antigens - metabolism; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Cell Biology; Cell Culture; Cell Fusion; Gene Expression Regulation; Giant Cells - metabolism; Giant Cells - pathology; HIV Envelope Protein gp160 - genetics; HIV Envelope Protein gp160 - metabolism; HIV Infections - genetics; HIV Infections - metabolism; HIV Infections - pathology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - metabolism; HIV-1 - pathogenicity; Host-Pathogen Interactions - genetics; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunology; Life Sciences; Protein Interaction Mapping; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; Receptors, Purinergic - genetics; Receptors, Purinergic - metabolism; Review; Signal Transduction - genetics
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2015.204

Infection by human immunodeficiency virus-1 (HIV-1) is associated with a progressive decrease in CD4 T-cell numbers and the consequent collapse of host immune defenses. The major pathogenic mechanism of AIDS is the massive apoptotic destruction of the immunocompetent cells, including uninfected cells. The latter process, also known as by-stander killing, operates by various mechanisms one of which involves the formation of syncytia which undergo cell death by following a complex pathway. We present here a detailed and curated map of the syncytial apoptosis signaling network, aimed at simplifying the whole mechanism that we have characterized at the molecular level in the last 15 years. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner software and encompasses 36 components (proteins/genes) and 54 interactions. The simplification of this complex network paves the way for the development of novel therapeutic strategies to eradicate HIV-1 infection. Agents that induce the selective death of HIV-1-elicited syncytia might lead to the elimination of viral reservoirs and hence constitute an important complement to current antiretroviral therapies.