Coronavirus interactions with the cellular autophagy machinery.

ABSTRACT

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is the most recent example of an emergent coronavirus that poses a significant threat to human health. Virus-host interactions play a major role in the viral life cycle and disease pathogenesis, and cellular pathways such as macroautophagy/autophagy prove to be either detrimental or beneficial to viral replication and maturation. Here, we describe the literature over the past twenty years describing autophagy-coronavirus interactions. There is evidence that many coronaviruses induce autophagy, although some of these viruses halt the progression of the pathway prior to autophagic degradation. In contrast, other coronaviruses usurp components of the autophagy pathway in a non-canonical fashion. Cataloging these virus-host interactions is crucial for understanding disease pathogenesis, especially with the global challenge of SARS-CoV-2 and COVID-19. With the recognition of autophagy inhibitors, including the controversial drug chloroquine, as possible treatments for COVID-19, understanding how autophagy affects the virus will be critical going forward. Abbreviations 3-MA 3-methyladenine (autophagy inhibitor); AKT/protein kinase B AKT serine/threonine kinase; ATG autophagy related; ATPase adenosine triphosphatase; BMM bone marrow macrophage; CGAS cyclic GMP-AMP synthase; CHO Chinese hamster ovary/cell line; CoV coronaviruses; COVID-19 Coronavirus disease 2019; DMV double-membrane vesicle; EAV equine arteritis virus; EDEM1 ER degradation enhancing alpha-mannosidase like protein 1; ER endoplasmic reticulum; ERAD ER-associated degradation; GFP green fluorescent protein; HCoV human coronavirus; HIV human immunodeficiency virus; HSV herpes simplex virus; IBV infectious bronchitis virus; IFN interferon; LAMP1 lysosomal associated membrane protein 1; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; MCoV mouse coronavirus; MERS-CoV Middle East respiratory syndrome coronavirus; MHV mouse hepatitis virus; NBR1 NBR1 autophagy cargo receptor; CALCOCO2/NDP52 calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp non-structural protein; OS9 OS9 endoplasmic reticulum lectin; PEDV porcine epidemic diarrhea virus; PtdIns3K class III phosphatidylinositol 3-kinase; PLP papain-like protease; pMEF primary mouse embryonic fibroblasts; SARS-CoV severe acute respiratory syndrome coronavirus; SKP2 S-phase kinase associated protein 2; SQSTM1 sequestosome 1; STING1 stimulator of interferon response cGAMP interactor 1; ULK1 unc-51 like autophagy activating kinase 1; Vps vacuolar protein sorting.