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Fig. 2.
Entry pathway of MHV and SARS-CoV. MHV S protein binds its
receptor CEACAM1 on the cell surface, and fusion of viral envelope and plasma
membrane takes place. Then, the genome is internalized directly into the cyto-
plasm through a plasma membrane. Possible entry mechanism of SARS-CoV is
as follows. SARS-CoV S protein binds ACE2, and the virion is incorporated
into the endosome by pinocytosis/endocytosis. Then, the endosome is fused
with lysosome, which provides the endosome with various proteases. Protease,
cathepsin L, reactive at a low pH environment activates the fusogenicity of
SARS-CoV S protein, facilitating viral envelope and endosomal membrane
fusion. Then, the SARS-CoV genome enters the cells via an endosomal membrane.
elastase. These proteases also induce fusion of SARS-CoV-infected
cells. The S proteins treated with these proteases show an indistinct
size of S protein, ca. 100 kDa.
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All of these data suggest that a pro-
tease reactive under low pH environment, most likely cathepsin L,
plays an important role in the entry mechanism of SARS-CoV.
Recently, we found that proteases that induce S protein cleavage as
well as fusion activity facilitate the entry of SARS-CoV from cell surface
by affecting the virion S proteins that bound to the receptor.
44
This
