Membrane remodeling by SARS-CoV-2 – double-enveloped viral replication

The ongoing pandemic of the new severe acute respiratory syndrome coronavirus (SARS-CoV-2) has caused more than one million deaths, overwhelmed many public health systems, and led to a worldwide economic recession. This has raised an unprecedented need to develop antiviral drugs and vaccines, which requires profound knowledge of the fundamental pathology of the virus, including its entry, replication, and release from host cells. The genome of coronaviruses comprises around 30 kb of positive single-stranded RNA, representing one of the largest RNA genomes of viruses. The 5′ part of the genome encodes a large polyprotein, PP1ab, which gives rise to 16 non-structural proteins (nsp1– nsp16). Two proteases encoded in nsp3 and nsp5 cleave the polyprotein into individual proteins. Most nsps belong to the viral replicase complex that promotes replication of the viral genome and translation of structural proteins by producing subgenomic mRNAs. The replicase complexes are found on double-membrane vesicles (DMVs) that contain viral double-stranded RNA. Expression of a small subset of viral proteins, including nsp3 and nsp4, is sufficient to induce formation of these DMVs in human cells, suggesting that both proteins deform host membranes into such structures. We will discuss the formation of DMVs and provide an overview of other membrane remodeling processes that are induced by coronaviruses.