Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/31660
Title: BIOCHEMICAL AND FUNCTIONAL CHARACTERISATIONS OF SARS-COV ACCESSORY PROTEINS: ORF 9B AND ORF6
Authors: CHEN GUANG
Keywords: SARS, Coronavirus, Characterisation, Accessory proteins, ORF9b, ORF6
Issue Date: 12-Sep-2011
Source: CHEN GUANG (2011-09-12). BIOCHEMICAL AND FUNCTIONAL CHARACTERISATIONS OF SARS-COV ACCESSORY PROTEINS: ORF 9B AND ORF6. ScholarBank@NUS Repository.
Abstract: The severe and acute respiratory syndrome (SARS) outbreak threatened the world in year 2003. SARS Coronavirus (SARS-CoV) was identified as the causative agent of this disease. SARS-CoV has evolved several novel proteins, which share no similarity with known proteins. In this study, SARS-CoV accessory proteins ORF9b and ORF6 were characterized. ORF9b was illustrated to undergo translation via ribosomal leaky scanning after the introduction of mutations to the context of the translation initiation sites. ORF9b was also demonstrated to facilitate virus assembly and release when it was co-expressed with structural protein M. ORF9b may carry out its functions via interaction with structural proteins E and M. ORF9b is incorporated into virion like particles as structural protein at presence of other structural proteins including M. H1299 cells with stable ORF6 expression, and Infectious Bronchitis Virus (IBV) with stable SARS-CoV ORF6 expression, were engineered. The gene profile in H1299-S6 was examined with microarray gene chip. ORF6 was shown to inhibit interferon production, and this inhibition may be caused by its interaction with IRF3. ORF6 doesn't prevent IRF3 phosphorylation, but prevents its entry into nucleus. ORF6 affects phosphorylation of STAT1, and was also shown to interfere with cell death. Microarray data also suggested that SARS-CoV ORF6 might interfere with other cell functions, like tissue morphology, molecular transport, nucleic acid metabolism and antigen presentation. Reverse genetic approach was used to generate recombinant Infectious Bronchitis Virus with foreign genes, and this method is a promising platform for gene delivery and vaccine development
URI: http://scholarbank.nus.edu.sg/handle/10635/31660
Appears in Collections:Ph.D Theses (Open)

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