Abstract

Autophagy is a protein degradative process important for normal cellular metabolism. It is apparently used also by cells to eliminate invading pathogens. Interestingly, many pathogens have learned to subvert the cell’s autophagic process. Here, we review the interactions between viruses and cells in regards to cellular autophagy. Using findings from hepatitis B virus and human retroviruses, HIV-1 and HTLV-1, we discuss mechanisms used by viruses to usurp cellular autophagy in ways that benefit viral replication. The term “autophagy” means “self-eating” derived from Greek. It was first mentioned by Christian De Duve in 1963, and has been used since to describe a bulk degradation process by lysosome-dependent mechanism. Autophagy functions to degrade protein aggregates, maintain the homeostasis of organelles, such as mitochondria, peroxisomes and ribosomes, and destroy intracellular pathogens. The selectivity of autophagic degradation is thought to be achieved by recognizing post-modification such as ubiquitination or acetylation on proteins. Several autophagy receptors or adaptors, including SQSTM1/p62, NBR1 and HDAC6, have been identified, and they are considered to function by recognizing and recruiting ubiquitinated protein aggregates to be degraded through the autophagy pathway.
The autophagy machinery contains more than 30 autophagy-related (Atg) genes; most of which are highly conserved from yeast to mammal. When autophagy is induced by stressed conditions such as starvation, the first step is the nucleation of phagophore membranes (Figure 1), also called pre-autophagosomal structures [10] or isolation membrane, which likely originates from the endoplasmic reticulum, Golgi complex, mitochondria, endosomes and/or the plasma membrane. The nucleation of phagophore membranes (pre-autophagosomal structures or isolation membrane): In nutrient rich condition, the mTORC1 kinase associates with the ULK1/2 complex to inhibit the initiation of autophagy. Under growth factor deprivation or nutrient starvation, energy sensor AMPK suppresses the activity of mTORC1 and activates the ULK1/2 complex which is essential for the induction of autophagy. The ULK1/2 complex likely recruits the Vps34-Beclin-1 complex to the site of autophagosome generation. (2) The formation of autophagosomes: