Lysosomal Proteases Are a Determinant of Coronavirus Tropism.
Identifieur interne : 001F76 ( Ncbi/Merge ); précédent : 001F75; suivant : 001F77Lysosomal Proteases Are a Determinant of Coronavirus Tropism.
Auteurs : Yuan Zheng [États-Unis] ; Jian Shang [États-Unis] ; Yang Yang [États-Unis] ; Chang Liu [États-Unis] ; Yushun Wan [États-Unis] ; Qibin Geng [États-Unis] ; Michelle Wang [États-Unis] ; Ralph Baric [États-Unis] ; Fang Li [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Cellules A549, Cellules HEK293, Cellules HeLa, Cellules Vero, Cellules cultivées, Chiroptera, Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme), Coronavirus du syndrome respiratoire du Moyen-Orient (physiologie), Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Infections à coronavirus (métabolisme), Lysosomes (enzymologie), Peptide hydrolases (métabolisme), Pénétration virale, Tropisme viral, Virus du SRAS (métabolisme), Virus du SRAS (physiologie).
- MESH :
- enzymologie : Lysosomes.
- métabolisme : Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Infections à coronavirus, Peptide hydrolases, Virus du SRAS.
- physiologie : Coronavirus du syndrome respiratoire du Moyen-Orient, Virus du SRAS.
- Animaux, Cellules A549, Cellules HEK293, Cellules HeLa, Cellules Vero, Cellules cultivées, Chiroptera, Humains, Pénétration virale, Tropisme viral.
English descriptors
- KwdEn :
- A549 Cells, Animals, Cells, Cultured, Chiroptera, Chlorocebus aethiops, Coronavirus Infections (metabolism), HEK293 Cells, HeLa Cells, Humans, Lysosomes (enzymology), Middle East Respiratory Syndrome Coronavirus (metabolism), Middle East Respiratory Syndrome Coronavirus (physiology), Peptide Hydrolases (metabolism), SARS Virus (metabolism), SARS Virus (physiology), Spike Glycoprotein, Coronavirus (metabolism), Vero Cells, Viral Tropism, Virus Internalization.
- MESH :
- chemical , metabolism : Peptide Hydrolases, Spike Glycoprotein, Coronavirus.
- enzymology : Lysosomes.
- metabolism : Coronavirus Infections, Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- physiology : Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- A549 Cells, Animals, Cells, Cultured, Chiroptera, Chlorocebus aethiops, HEK293 Cells, HeLa Cells, Humans, Vero Cells, Viral Tropism, Virus Internalization.
Abstract
Cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. Despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. Here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, using the spike proteins from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) as the model system. To this end, we controlled the contributions from receptor binding and other host proteases, thereby attributing coronavirus entry solely or mainly to the efficiency of lysosomal proteases in activating coronavirus spike-mediated membrane fusion. Our results showed that lysosomal proteases from bat cells support coronavirus spike-mediated pseudovirus entry and cell-cell fusion more effectively than their counterparts from human cells. Moreover, purified lysosomal extracts from bat cells cleave cell surface-expressed coronavirus spikes more efficiently than their counterparts from human cells. Overall, our study suggests that different lysosomal protease activities from different host species and tissue cells are an important determinant of the species and tissue tropism of coronaviruses.IMPORTANCE Coronaviruses are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.
DOI: 10.1128/JVI.01504-18
PubMed: 30258004
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<front><div type="abstract" xml:lang="en">Cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. Despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. Here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, using the spike proteins from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) as the model system. To this end, we controlled the contributions from receptor binding and other host proteases, thereby attributing coronavirus entry solely or mainly to the efficiency of lysosomal proteases in activating coronavirus spike-mediated membrane fusion. Our results showed that lysosomal proteases from bat cells support coronavirus spike-mediated pseudovirus entry and cell-cell fusion more effectively than their counterparts from human cells. Moreover, purified lysosomal extracts from bat cells cleave cell surface-expressed coronavirus spikes more efficiently than their counterparts from human cells. Overall, our study suggests that different lysosomal protease activities from different host species and tissue cells are an important determinant of the species and tissue tropism of coronaviruses.<b>IMPORTANCE</b>
Coronaviruses are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.</div>
</front>
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<Abstract><AbstractText>Cell entry by coronaviruses involves two principal steps, receptor binding and membrane fusion; the latter requires activation by host proteases, particularly lysosomal proteases. Despite the importance of lysosomal proteases in both coronavirus entry and cell metabolism, the correlation between lysosomal proteases and cell tropism of coronaviruses has not been established. Here, we examined the roles of lysosomal proteases in activating coronavirus surface spike proteins for membrane fusion, using the spike proteins from severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) as the model system. To this end, we controlled the contributions from receptor binding and other host proteases, thereby attributing coronavirus entry solely or mainly to the efficiency of lysosomal proteases in activating coronavirus spike-mediated membrane fusion. Our results showed that lysosomal proteases from bat cells support coronavirus spike-mediated pseudovirus entry and cell-cell fusion more effectively than their counterparts from human cells. Moreover, purified lysosomal extracts from bat cells cleave cell surface-expressed coronavirus spikes more efficiently than their counterparts from human cells. Overall, our study suggests that different lysosomal protease activities from different host species and tissue cells are an important determinant of the species and tissue tropism of coronaviruses.<b>IMPORTANCE</b>
Coronaviruses are capable of colonizing new species, as evidenced by the recent emergence of SARS and MERS coronaviruses; they can also infect multiple tissues in the same species. Lysosomal proteases play critical roles in coronavirus entry by cleaving coronavirus surface spike proteins and activating the fusion of host and viral membranes; they also play critical roles in cell physiology by processing cellular products. How do different lysosomal protease activities from different cells impact coronavirus entry? Here, we controlled the contributions from known factors that function in coronavirus entry so that lysosomal protease activities became the only or the main determinant of coronavirus entry. Using pseudovirus entry, cell-cell fusion, and biochemical assays, we showed that lysosomal proteases from bat cells activate coronavirus spike-mediated membrane fusion more efficiently than their counterparts from human cells. Our study provides the first direct evidence supporting lysosomal proteases as a determinant of the species and tissue tropisms of coronaviruses.</AbstractText>
<CopyrightInformation>Copyright © 2018 American Society for Microbiology.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Zheng</LastName>
<ForeName>Yuan</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, Minnesota, USA.</Affiliation>
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<affiliations><list><country><li>États-Unis</li>
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