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.
|
Authors | S L Alan Wong, Yiwei Chen, Chak Ming Chan, C S Michael Chan, Paul K S Chan, Y L Chui, Kwok Pui Fung, Mary M Y Waye, Stephen K W Tsui, H Y Edwin Chan |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 337
Issue 2
Pg. 720-9
(Nov 18 2005)
ISSN: 0006-291X [Print] United States |
PMID | 16212942
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- 3a protein, SARS-CoV
- Antibodies, Monoclonal
- Clathrin
- Viral Envelope Proteins
- Viral Proteins
- Viroporin Proteins
|
Topics |
- Animals
- Animals, Genetically Modified
- Antibodies, Monoclonal
(immunology)
- Clathrin
(metabolism)
- Cytoplasm
(metabolism)
- Drosophila
(genetics)
- Endocytosis
- Gene Transfer Techniques
- Humans
- Phenotype
- Severe acute respiratory syndrome-related coronavirus
(genetics)
- Viral Envelope Proteins
- Viral Proteins
(genetics, metabolism)
- Viroporin Proteins
|