ABSTRACT
Coronaviruses (CoVs) assemble by budding into the lumen of the intermediate compartment (IC) at the endoplasmic reticulum (ER)-Golgi interface. However, why CoVs have chosen the IC as their intracellular site of assembly and how progeny viruses are delivered from this compartment to the extracellular space has remained unclear. Here we address these enigmatic late events of the CoV life cycle in light of recently described properties of the IC. Of particular interest are the emerging spatial and functional connections between IC elements and recycling endosomes (REs), defined by the GTPases Rab1 and Rab11, respectively. The establishment of IC-RE links at the cell periphery, around the centrosome and evidently also at the noncompact zones of the Golgi ribbon indicates that-besides traditional ER-Golgi communication-the IC also promotes a secretory process that bypasses the Golgi stacks, but involves its direct connection with the endocytic recycling system. The initial confinement of CoVs to the lumen of IC-derived large transport carriers and their preferential absence from Golgi stacks is consistent with the idea that they exit cells following such an unconventional route. In fact, CoVs may share this pathway with other intracellularly budding viruses, lipoproteins, procollagen, and/or protein aggregates experimentally introduced into the IC lumen.
Subject(s)
Endoplasmic Reticulum/virology , Extracellular Space/virology , Golgi Apparatus/virology , Intracellular Membranes/virology , SARS-CoV-2/physiology , Secretory Pathway , Virus Release , Animals , COVID-19/therapy , COVID-19/virology , Centrosome/metabolism , Extracellular Space/metabolism , Golgi Apparatus/metabolism , Humans , Protein TransportSubject(s)
Cilia/metabolism , Eye Diseases/metabolism , Flagella/metabolism , Heart Diseases/metabolism , Lung Diseases/metabolism , Polycystic Kidney Diseases/metabolism , Centrosome/metabolism , Centrosome/ultrastructure , Cilia/ultrastructure , Epithelial Cells/metabolism , Epithelial Cells/ultrastructure , Eye Diseases/genetics , Eye Diseases/pathology , Flagella/ultrastructure , Gene Expression Regulation , Heart Diseases/genetics , Heart Diseases/pathology , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Humans , Lung Diseases/genetics , Lung Diseases/pathology , Polycystic Kidney Diseases/genetics , Polycystic Kidney Diseases/pathology , Wnt Signaling PathwayABSTRACT
The novel coronavirus SARS-CoV-2 is the causative agent of the global coronavirus disease 2019 (COVID-19) outbreak. In addition to pneumonia, other COVID-19-associated symptoms have been reported, including loss of smell (anosmia). However, the connection between infection with coronavirus and anosmia remains enigmatic. It has been reported that defects in olfactory cilia lead to anosmia. In this Viewpoint, we summarize transmission electron microscopic studies of cilia in virus-infected cells. In the human nasal epithelium, coronavirus infects the ciliated cells and causes deciliation. Research has shown that viruses such as influenza and Sendai attach to the ciliary membrane. The Sendai virus enters cilia by fusing its viral membrane with the ciliary membrane. A recent study on SARS-CoV-2-human protein-protein interactions revealed that the viral nonstructural protein Nsp13 interacts with the centrosome components, providing a potential molecular link. The mucociliary escalator removes inhaled pathogenic particles and functions as the first line of protection mechanism against viral infection in the human airway. Thus, future investigation into the virus-cilium interface will help further the battle against COVID-19.