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In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila.

Identifieur interne : 004790 ( Main/Exploration ); précédent : 004789; suivant : 004791

In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila.

Auteurs : S L Alan Wong [République populaire de Chine] ; 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

Source :

RBID : pubmed:16212942

Descripteurs français

English descriptors

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.

DOI: 10.1016/j.bbrc.2005.09.098
PubMed: 16212942


Affiliations:


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<div type="abstract" xml:lang="en">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.</div>
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