Role of autophagy in HIV infection and pathogenesis

Abstract

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.

Impact of the host environment on the antitubercular action of pyrazinamide

“…Some studies have suggested that PZA potentiation by the host may be related to drug upregulation of the autophagy pathway [96] . Multiple studies have reported the occurrence of dysregulated autophagy during diseases that cause altered immune states [97][98][99][100] While many outstanding questions remain, these studies indicate that the appropriate cell-mediated responses are critical for optimal PZA efficacy, and both local and systemic immune modulation are highly impactful for PZA efficacy.…”

The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections

“…The aim of autophagy is to reestablish homeostasis in response to a variety of stress conditions. 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 chronic infection [324]. HIV infection has been shown to induce and inhibit autophagy.…”

“…Tat inhibits autophagy in neurons and also inhibits autophagosome/lysosome fusion by interaction with LAMP2A; this might be the reason that neurons will proceed to apoptosis because of inhibition of autophagy in HIV-associated neurodegenerative disease (HAND). Tat induces autophagy by interaction with BAG3 in glial cells [324]. Nef, an HIV-1 accessory protein, interacts with IRGM and then IRGM is capable of activating autophagy by favoring the assembly of a ULK1/BECLIN-1/ATG16 complex.…”

“…Although autophagy levels are upregulated during infection, both antiviral and immune properties of this process are severely inhibited by HIV infection. An important example is the interaction of Nef and Beclin-1 which inhibits autophagosome maturation [324].…”

Introduction to Nobel Conference: ‘The Cell Cycle and Cell Death in Disease’

“…In two review articles, various aspects of the relationship between cell death mechanisms and HIV are discussed. Thus, Nardacci et al present evidence for role of autophagy in HIV infection and pathogenesis [3]. HIV infection represents a system in which a virus via several strategies deactivates the autophagy.…”