SARS coronavirus entry into host cells through a novel clathrin- and caveolae-independent endocytic pathway

当严重急性呼吸症候群日冕病毒(SARS-CoV ) 开始被认为与质膜通过直接熔化进入房间时，更最近的证据建议那个病毒条目可以也包含 endocytosis。我们发现了那 SARS-CoV 进入房间经由 pH 依赖并且受体依赖者 endocytosis。有任何一个 SARS-CoV 尖铁蛋白质或忍受尖铁的假病毒的房间的治疗导致了变换血管收缩素的酶的 translocation 2 (ACE2 ) ， SARS-CoV 的功能的受体，从房间表面到内涵体。另外，忍受尖铁的假病毒和 1 在内涵体被发现到 colocalize 的早内涵体抗原。用象 caveolin-1 colocalization 学习一样的特定的 endocytic 小径禁止者和主导否定的 Eps15 的进一步的分析建议那个病毒条目被 clathrin 独立、 caveolae 独立的机制调停。而且，在质膜的微域，它被显示出到为许多生理的发信号小径作为平台扮演的充满胆固醇、 sphingolipid 富有的类脂化合物木排，被显示涉及病毒入口。SARS-CoV 的 Endocytic 入口可以扩展这里的 SARS-CoV 感染，和我们的调查结果的细胞的范围贡献 SARS-CoV 致病的理解，为抗病毒的药研究提供新信息。

While severe acute respiratory syndrome coronavirus （SARS-CoV）~as initially thought to enter cells through direct fusion with the plasma membrane, more recent evidence suggests that yirus entry may also involve endocytosis. We have found that SARS-CoV enters cells viapH- 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 path- way inhibitors and dominant-negative Epsl5 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.