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6. Roles of spike protein in the pathogenesis of SARS coronavirus   Funds : Research Fund for the Control of Infectious Diseases (investigator-initiated projects) Project Status : Closed Reference No. : 01030222 Project Title : Roles of spike protein in the pathogenesis of SARS coronavirus Applicant(s) : Jin DY Zheng BJ Affiliation(s) : The University of Hong Kong Approved Amount (HK$) : $805,000.00 Abstract : Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with pneumonia and it has affected Hong Kong, China and the rest of the world. SARS is etiologically associated with a previously unrecognized RNA virus in the Coronaviridae family. This virus designated SARS coronavirus (SARS-CoV) is classified into a new subgroup, which is distinct from the other coronaviruses but was also believed to be most closely related to group 2. Among the various structural and nonstructural proteins of SARS-CoV, the spike (S) protein is a large and multifunctional protein that plays pivotal roles in the pathogenesis of viral infection. In particular, S is thought to mediate receptor binding and to induce membrane fusion. In response to the emergency of SARS outbreak in Hong Kong, we have obtained more than 30 isolates of SARS-CoV from human patients and from small wild animals. We have also cloned the S gene from several isolates of SARS-CoV. In this study we will take a molecular approach to characterizing the properties of SARS-CoV S protein in cultured mammalian cells and thereby shedding light on its roles in the pathogenesis of SARS. First, we will investigate whether and how S is cleaved. We will also assess the oligomerization state, subcellular localization and surface expression of S. Second, we will investigate the identity of the cellular receptor or co-receptor of SARS-CoV. This will help define the molecular basis for species and tissue tropism. Third, we will develop assays to examine whether and how S induces cell-to-cell fusion. Finally, we will explore the pathological effects of S on the cell. Specifically, we will investigate the ability of S to induce endoplasmic reticulum (ER) stress and to activate NFkB. Our study has the potential to derive novel and important insights into the molecular mechanisms for SARS-CoV pathogenesis and to reveal novel strategies for prevention as well as therapeutic interventions of SARS. Keywords : SARS, SARS coronavirus, spike protein, coronavirus receptor, membrane fusion, species tropism, tissue tropism, cell-to-cell fusion, ER stress, NFkB Instruments : Remarks : [add to bookmark]

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Last revision date: 15 August 2006