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Wang, H, Yang, P, Liu, K, Guo, F, Zhang, Y, Zhang, Get al.. SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway. Cell Res 18: 290-301

National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Tsinghua University and Chinese Academy of Medical Sciences, Beijing 100005, China.
Cell Research (Impact Factor: 11.98). 03/2008; 18(2):290-301. DOI: 10.1038/cr.2008.15
Source: PubMed

ABSTRACT While severe acute respiratory syndrome coronavirus (SARS-CoV) was initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that virus entry may also involve endocytosis. We have found that SARS-CoV enters cells via pH- and receptor-dependent endocytosis. Treatment of cells with either SARS-CoV spike protein or spike-bearing pseudoviruses resulted in the translocation of angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV, from the cell surface to endosomes. In addition, the spike-bearing pseudoviruses and early endosome antigen 1 were found to colocalize in endosomes. Further analyses using specific endocytic pathway inhibitors and dominant-negative Eps15 as well as caveolin-1 colocalization study suggested that virus entry was mediated by a clathrin- and caveolae-independent mechanism. Moreover, cholesterol- and sphingolipid-rich lipid raft microdomains in the plasma membrane, which have been shown to act as platforms for many physiological signaling pathways, were shown to be involved in virus entry. Endocytic entry of SARS-CoV may expand the cellular range of SARS-CoV infection, and our findings here contribute to the understanding of SARS-CoV pathogenesis, providing new information for anti-viral drug research.

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Available from: Yanli Zhang, Aug 31, 2015
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    • "There is some debate as to where fusion occurs with wild-type SARS-coronavirus. Initially, it was thought to enter cells through direct fusion with the plasma membrane;40 however, more recent evidence suggests that virus entry may also involve pH-dependent endocytosis.41 Of the envelope glycoproteins listed, only FIV pseudotyped with VSVG and GP64 have been demonstrated to transduce cells via a low-pH endosome route.30 "
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    11/2012; 1(11):e56. DOI:10.1038/mtna.2012.47
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    • "In addition to replication-competent viruses, pseudoviruses have become an ideal tool to investigate cell entry of SARS-CoV without safety concerns [22], [25], [26]. SARS pseudovirus possesses the morphological characteristics of replication-competent SARS-CoV, with SARS-CoV spike protein on the envelope membrane, and can mimic SARS-CoV in the process of cell entry. "
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    PLoS ONE 08/2011; 6(8):e23710. DOI:10.1371/journal.pone.0023710 · 3.23 Impact Factor
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    • "A number of caveolin-independent pathways also originate from lipid-rafts, and novel clathrin- and raft-independent processes have also been identified. These pathways have different requirements for cellular proteins such as dynamin, flotillin, small GTPases, and for cholesterol and other specific lipids [1], [2], [19], [20], [21], [22], [23], [24], [25], and can also be exploited by viruses for infection [21], [26], [27], [28], [29], [30], [31]. "
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