published_or_final_version / Statistics and Actuarial Science / Doctoral / Doctor of Philosophy

published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Coronaviruses are a diverse group of large, single-stranded RNA virus that cause respiratory and enteric diseases in mammalian and avian species. Phylogenetic analysis shows that SARS-CoV is an unique branch of coronavirus showing no close relationship to other groups of coronaviruses. The genome size of SARS-CoV is about 30 kilobase and the genome, like other coronaviruses, is composed of replicase (rep), spike (S), envelope (E), membrane (M) and nucleocapsid (N) and 8 additional unknown open reading frames (ORFs) (ORF 3a, ORF 3b, ORF 6, ORF 7a, ORF 7b, ORF8a, ORF 8b and ORF 9b). The 3a gene, the largest unknown ORF, encodes a viral protein which is predicted to be a transmembrane protein. In this study, we showed that the 3a protein was expressed in SARS patients' lung and intestinal tissues, and it is localized to the endoplasmic reticulum (ER) in 3a-transfected monkey kidney Vero E6 cells. Results from experiments including chromatin condensation, DNA fragmentation and antibody microarray suggest that the 3a protein may trigger apoptosis through a caspase-8-dependent pathway and possibly a PKR-mediated FADD-caspase-8 pathway. Our data show that over-expression of the SARS-CoV protein can induce apoptosis in vitro. / Severe acute respiratory syndrome (SARS), an atypical form of pneumonia, is first recognized in Guangdong Province, China in November 2002 and later spread to Hong Kong in mid February 2003. It is believed that the etiological agent of SARS is a previously unknown coronavirus - SARS-CoV. Over 8,400 cases and 789 deaths were reported to World Health Organization (WHO) from over 28 countries around the world including Hong Kong. Up to now, there are still no efficient antiviral drugs to treat the disease, and the detailed pathology of SARS-CoV infection and the host response to the viral infection are still unknown. During the epidemic, we have done complete genome sequencing for five SARS-CoV isolates and we postulate that at least two SARS-CoV strains with distinct etiological origins exist in the environment during the epidemic. / Law Tit-wan Patrick. / "Aug 2005." / Adviser: Stephen K. W. Tsui. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3594. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 156-172). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.