Figure 1.

The SARS-CoV-2 infection cycle and the production of EVs. There are two distinct SARS-CoV-2 entry pathways. (1) CD9 works with TMPRSS2 to cleave viral fusion glycoproteins, facilitating coronavirus entrance. Alternatively, the virus binds to the ACE2 receptor in the lipid rafts region, where the virus–ACE2 complex is internalized via endocytosis. (2) The infection with a coronavirus causes the creation of new membrane structures of various sizes and forms in the perinuclear area, which are collectively referred to as replication organelles. Viral structural proteins and genomic RNA are produced at the replication site and subsequently translocated to the ER-Golgi intermediate compartment (ERGIC), where virus assembly and budding occur via an unknown mechanism. New viruses from the ERGIC lumen bud into the secretory route and reach the plasma membrane, where they are released into the extracellular environment after virus-containing vesicles fuse with the plasma membrane. In parallel, (3) SARS-CoV-2 arrives at lysosomes via the late endosome and (4) multivesicular bodies (MVBs), forming exosomes containing viral cargo (5), which are released into the extracellular environment. In parallel, EVs can be internalized by clathrin-mediated endocytosis (6). In detail, EVs carry proteins such as MHC, Tetraspanin, ACE2 and flotillin on their membrane while also containing viral and host cell components internally.