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|Title:||Interaction of SARS-CoV spike protein with lipid rafts of host cells during viral entry||Authors:||Lu, Yanning||Keywords:||DRNTU::Science::Biological sciences::Microbiology::Virology||Issue Date:||2007||Source:||Lu, Y. N. (2007). Interaction of SARS-CoV spike protein with lipid rafts of host cells during viral entry. Doctoral thesis, Nanyang Technological University, Singapore.||Abstract:||SARS-CoV entry is mediated by S protein. ACE2 has been identified as its receptor. During viral entry, interactions between a virus and host cell surface receptors play a key role in successful infection. In addition, many viruses such as HIV-1, select special membrane domains named as lipid rafts that are rich in sphingolipids, glycosphingolipids and cholesterol as entry sites, either as signaling platforms or as concentration devices. Here I report that the integrity of lipid rafts is required for productive infection of pseudotyped SARS-CoV, depletion of cholesterol inhibits the infection by 90%. ACE2 colocalizes with lipid rafts and S protein ectodomain associates with lipid rafts after binding ACE2, which strongly support that lipid rafts serve as an entry port for SARS-CoV. The role of S protein Trp-rich region in viral entry was further investigated. Mutations of Trp with Ala dramatically decrease the infectivity of pseudotyped SARS-CoV, suggesting the importance of this region. Finally, peptide library was screened using S protein ectodomain. The self-interacting peptides are largely limited to the exposed surfaces with ordered structure of a-helices and ?-sheets located in receptor-binding domain and HR1 regions. Taken together, these findings provide useful clues for understanding the entry mechanism and developing potential therapeutics for SARS-CoV.||URI:||https://hdl.handle.net/10356/6585||DOI:||10.32657/10356/6585||Rights:||Nanyang Technological University||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Theses|
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