Abstract
The mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) egress, similar to those of other coronaviruses, remain poorly understood. The virus buds in intracellular compartments and is therefore thought to be released by the biosynthetic secretory pathway. However, several studies have recently challenged this hypothesis. It has been suggested that coronaviruses, including SARS-CoV-2, use lysosomes for egress. In addition, a focused ion-beam scanning electron microscope (FIB/SEM) study suggested the existence of exit tunnels linking cellular compartments rich in viral particles to the extracellular space resembling those observed for the human immunodeficiency (HIV) in macrophages. Here, we analysed serial sections of Vero cells infected with SARS-CoV-2 by transmission electron microscopy (TEM). We found that SARS-CoV-2 was more likely to exit the cell in small secretory vesicles. Virus trafficking within the cells involves small vesicles, with each generally containing a single virus particle. These vesicles then fuse with the plasma membrane to release the virus into the extracellular space. This work sheds new light on the late stages of the SARS-CoV-2 infectious cycle of potential value for guiding the development of new antiviral strategies.
Highlights
The world is currently in the grip of a pandemic of coronavirus disease 19 (COVID19), a new transmissible infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Coronaviruses have previously been observed in lysosomal compartments on transmission electron microscopy (TEM), but the significance of these observations remained unexplored at the time [12]
Using conventional TEM, we recently described the ultrastructural characteristics of the complete infectious cycle of SARS-CoV-2 within the host cell [14]
Summary
The world is currently in the grip of a pandemic of coronavirus disease 19 (COVID19), a new transmissible infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The translation of the positive-sense sub-genomic viral RNA results in the synthesis of all viral proteins, including those necessary for the morphogenesis of progeny virions These viral particles, similar to those of other coronaviruses, are predominantly spherical or ellipsoidal, with a mean diameter between 90 and 100 nm [6,7]. Coronaviruses have previously been observed in lysosomal compartments on transmission electron microscopy (TEM), but the significance of these observations remained unexplored at the time [12] It is unknown whether these intracellular compartments containing viral particles can fuse with the plasma membrane for virion release. We did not observe any opening of intracellular virus-rich cisterns to the extracellular space We conclude from these TEM observations that SARS-CoV-2 is probably released from its host cell in small secretory vesicles
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