Back to Search Start Over

Lysosomal Proteases Are a Determinant of Coronavirus Tropism.

Authors :
Yuan Zheng
Jian Shang
Yang Yang
Chang Liu
Yushun Wan
Qibin Geng
Wang, Michelle
Baric, Ralph
Fang Li
Source :
Journal of Virology. Dec2018, Vol. 92 Issue 24, p1-14. 14p.
Publication Year :
2018

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0022538X
Volume :
92
Issue :
24
Database :
Academic Search Index
Journal :
Journal of Virology
Publication Type :
Academic Journal
Accession number :
133373436
Full Text :
https://doi.org/10.1128/JVI.01504-18