1. In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila
- Author
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Wong, S.L. Alan, Chen, Yiwei, Chan, Chak Ming, Chan, C.S. Michael, Chan, Paul K.S., Chui, Y.L., Fung, Kwok Pui, Waye, Mary M.Y., Tsui, Stephen K.W., and Chan, H.Y. Edwin
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DROSOPHILA , *MOLECULAR cloning , *APOPTOSIS , *MONOCLONAL antibodies - Abstract
Abstract: The Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3a locus encodes a 274 a.a. novel protein, and its expression has been confirmed in SARS patients. To study functional roles of 3a, we established a transgenic fly model for the SARS-CoV 3a gene. Misexpression of 3a in Drosophila caused a dominant rough eye phenotype. Using a specific monoclonal antibody, we demonstrated that the 3a protein displayed a punctate cytoplasmic localization in Drosophila as in SARS-CoV-infected cells. We provide genetic evidence to support that 3a is functionally related to clathrin-mediated endocytosis. We further found that 3a misexpression induces apoptosis, which could be modulated by cellular cytochrome c levels and caspase activity. From a forward genetic screen, 78 dominant 3a modifying loci were recovered and the identity of these modifiers revealed that the severity of the 3a-induced rough eye phenotype depends on multiple cellular processes including gene transcriptional regulation. [Copyright &y& Elsevier]
- Published
- 2005
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