title: The role and therapeutic potential of autophagy modulation in controlling virus-induced cell death.
abstract: Macroautophagy (hereafter referred to as autophagy) is an evolutionary conserved catabolic process in which the cytoplasmic content is sequestered and degraded by the lysosomal machinery in order to maintain cellular homeostasis or provide energy during metabolic and hypoxic stress. It also represents an important component of the host response against infectious agents, performing surveillance and effector functions involved in detection and clearance of pathogens, including viruses. Moreover, it appears that autophagy plays a major role in determining the fate of both virally infected and uninfected cells by blocking or promoting their death in a virus- and cell-type-dependent manner. We here review the current knowledge on the complex involvement of autophagy in survival and death of the host cells during viral infection, focusing on the molecular mechanisms underlying viral modulation of autophagic response and its interference with the cell death pathways. We also discuss a possible significance of the autophagy-dependent modulation of cell death for the outcome and therapy of viral infections, emphasizing the need for a time- and cell-type-dependent fine-tuning of the autophagic response in achieving an optimal balance between beneficial and adverse effects.
authors.affiliation: Institute for Biological Research, University of Belgrade, Despot Stefan Boulevard 142, 11000, Belgrade, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Tovilovic
authors.forename: Biljana
authors.initials: B
authors.lastname: Ristic
authors.forename: Marina
authors.initials: M
authors.lastname: Milenkovic
authors.forename: Maja
authors.initials: M
authors.lastname: Stanojevic
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajkovic
mesh_terms: D000818:Animals; D001343:Autophagy; D006801:Humans; D014777:Virus Diseases / Q000473:pathology* / Q000628:therapy*; D014780:Viruses / Q000378:metabolism*
keywords: apoptosis; autophagy; cell death; therapy; virus