In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila
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...
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Veröffentlicht in: | Biochemical and biophysical research communications 2005-11, Vol.337 (2), p.720-729 |
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Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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 3
a-induced rough eye phenotype depends on multiple cellular processes including gene transcriptional regulation. |
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ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2005.09.098 |