Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner

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Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. In the present study we investigated the entry of coronaviruses (CoVs). CoVs are important pathogens of animals and man with high zoonotic potential as demonstrated by the emergence of SARS- and MERS-CoVs. Previous studies resulted in apparently conflicting results with respect to CoV cell entry, particularly regarding the fusion-activating requirements of the CoV S protein. By combining cell-biological, infection, and fusion assays we demonstrated that murine hepatitis virus (MHV), a prototypic member of the CoV family, enters cells via clathrin-mediated endocytosis. Moreover, although MHV does not depend on a low pH for fusion, the virus was shown to rely on trafficking to lysosomes for proteolytic cleavage of its spike (S) protein and membrane fusion to occur. Based on these results we predicted and subsequently demonstrated that MERS- and feline CoV require cleavage by different proteases and escape the endo/lysosomal system from different compartments. In conclusion, we elucidated the MHV entry pathway in detail and demonstrate that a proteolytic cleavage site in the S protein of different CoVs is an essential determinant of the intracellular site of fusion.

Vyšlo v časopise: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004502
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004502

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