Role of autophagy in HIV infection and pathogenesis

• Published in: Journal of internal medicine Vol. 281; no. 5; pp. 422 - 432
• Main Authors: Nardacci, R., Ciccosanti, F., Marsella, C., Ippolito, G., Piacentini, M., Fimia, G. M.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2017
• Subjects: Adaptive immunity; Autophagy; Autophagy - physiology; Autophagy-Related Proteins - immunology; CD4-Positive T-Lymphocytes - immunology; Cell cycle; Cell death; Central Nervous System Infections - immunology; Chronic infection; Damage; Degradation; Degradation products; Dendritic Cells - immunology; Drugs; HIV; HIV - immunology; HIV - physiology; HIV Infections - immunology; Homeostasis; Human immunodeficiency virus; Humans; Immune response; Immune system; Immunity; Immunity, Cellular - immunology; Immunosuppressive agents; Infections; inflammation; Lysosomes; Macrophages - immunology; Membrane vesicles; Molecular modelling; Nef protein; Pathogenesis; Pathogens; Phagocytosis; Proteins; Tat protein; TOR protein; Virus Replication - physiology; Viruses; autophagy; HIV; cell death; inflammation
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/joim.12596

The aim of autophagy is to re‐establish homeostasis in response to a variety of stress conditions. By forming double‐membrane vesicles, autophagy engulfs damaged or superfluous cytoplasmic material and recycles degradation products for new synthesis or energy production. Of note, the same mechanism is used to capture pathogens and has important implications in both innate and adaptive immunity. To establish a chronic infection, pathogens have therefore evolved multiple mechanisms to evade autophagy‐mediated degradation. HIV infection represents one of the best characterized systems in which autophagy is disarmed by a virus using multiple strategies to prevent the sequestration and degradation of its proteins and to establish a chronic infection. HIV alters autophagy at various stages of the process in both infected and bystander cells. In particular, the HIV proteins TAT, NEF and ENV are involved in this regulation by either blocking or stimulating autophagy through direct interaction with autophagy proteins and/or modulation of the mTOR pathway. Although the roles of autophagy during HIV infection are multiple and vary amongst the different cell types, several lines of evidence point to a potential beneficial effect of stimulating autophagy‐mediated lysosomal degradation to potentiate the immune response to HIV. Characterization of the molecular mechanisms regulating selective autophagy is expected to be valuable for developing new drugs able to specifically enhance the anti‐HIV response. Content List – Read more articles from the symposium: Nobel Conference: Cell Cycle and Cell Death in Disease.