Bidirectional interplay between SARS-CoV-2 and autophagy

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the causative agent of the recent COVID-19 pandemic, continues representing one of the main health concerns worldwide. Autophagy, in addition to its role in cellular homeostasis and metabolism, plays an important part for the host antiviral immunity. However, viruses including SARS-CoV-2 have evolved diverse mechanisms to not only overcome autophagy’s antiviral pressure but also manipulate its machinery in order to enhance viral replication and propagation. Here, we discuss our current knowledge on the impact that autophagy exerts on SARS-CoV-2 replication, as well as the different counteracting measures that this virus has developed to manipulate autophagy’s complex machinery. Some of the elements regarding this interplay may become future therapeutic targets in the fight against SARS-CoV-2.

Autophagy as an innate immunity response against pathogens: a Tango dance

“…Despite an important interplay between CoVs and the ATG machinery, DMVs in cells infected with CoVs, such as MHV, SARS-CoV and SARS-CoV-2, are not generated by the canonical ATG machinery [223,228,229]. The current idea about the relationship between CoVs and autophagy, mostly coming from recent studies on SARSCoV-2, is that autophagy is induced, but CoVs subvert this pathway by avoiding the autophagosome-lysosome fusion, hence lysosomal degradation [230].…”

“…The afore mentioned cases are just mere examples (Table 4); for exhaustive recent revisions on the topic, including plant viruses, please refer to [224][225][226][227][228][229][230][231][232][233][234][235][236][237][238][239].…”

“…Hijack of the autophagosomal membranes [223][224][225][226][227][228][229][230] interactions, to emphasize their complexity (Tables 1-4). Nevertheless, it is important to consider that even though the specific molecular details have perhaps been identified for only one defined event, pro-and antipathogen pathways are probably active concurrently in each host-pathogen interaction situation.…”