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This suggests that SARS-CoV bearing a cleaved form of the S protein can enter cells directly from the cell surface without trypsin treatment. To explore this possibility, we introduced a furin-like cleavage sequence in the S protein at amino acids 798 to 801 and found that the mutated S protein was cleaved and induced cell fusion without trypsin treatment when expressed on the cell surface. Furthermore, a pseudotype virus bearing a cleaved S protein was revealed to infect cells in the presence of a lysosomotropic agent as well as a protease inhibitor, both of which are known to block SARS-CoV infection via an endosome, whereas the infection of pseudotypes with an uncleaved, wild-type S protein was blocked by these agents. A heptad repeat peptide, derived from a SARS-CoV S protein that is known to efficiently block infections from the cell surface, blocked the infection by a pseudotype with a cleaved S protein but not that with an uncleaved S protein. Those results indicate that SARS-CoV with a cleaved S protein is able to enter cells directly from the cell surface and agree with the previous observation of the protease-mediated cell surface entry of SARS-CoV.<\/jats:p>","DOI":"10.1128\/jvi.01412-08","type":"journal-article","created":{"date-parts":[[2008,9,12]],"date-time":"2008-09-12T00:35:58Z","timestamp":1221179758000},"page":"11985-11991","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":78,"title":["Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus with Cleaved S Protein as Revealed by Pseudotype Virus Bearing Cleaved S Protein"],"prefix":"10.1128","volume":"82","author":[{"given":"Rie","family":"Watanabe","sequence":"first","affiliation":[{"name":"Departments of Virology III"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shutoku","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Departments of Virology III"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Shirato","sequence":"additional","affiliation":[{"name":"Departments of Virology III"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Maejima","sequence":"additional","affiliation":[{"name":"Departments of Virology III"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuetsu","family":"Fukushi","sequence":"additional","affiliation":[{"name":"I, National Institute of Infectious Diseases, Murayama Branch, Musashi-Murayama, Tokyo 208-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Morikawa","sequence":"additional","affiliation":[{"name":"I, National Institute of Infectious Diseases, Murayama Branch, Musashi-Murayama, Tokyo 208-0011, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiro","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Departments of Virology III"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"118","volume":"52","year":"2008","unstructured":"Ami, Y., N. 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