Interaction of SARS-CoV spike protein with lipid rafts of host cells during viral entry.
Date of Issue2007
School of Biological Sciences
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.
Nanyang Technological University