The molecular cell death mechanism induced by grouper sea perch iridovirus (GSIV) serine theroine kinase gene in grouper fish cells

  • 巫 瑞旭

Student thesis: Doctoral Thesis


Abstract Aquaculture is one of the most important economic activities in Asia and is presently the fastest growing sector of food production in the world Explosive increases in global fish farming have been accompanied by an increase in viral diseases Viral infections are responsible for huge economic losses in fish farming and control of these viral diseases in aquaculture remains a serious challenge The prevention and treatment of viral infections are particularly challenging because viruses use the host cell machinery to replicate and interrupting viral replication without damaging host cell structures or processes presents a puzzle Thus the development of antiviral vaccines or drugs requires an understanding of both the host immune system genetics and viral gene function Apoptosis plays a central role in the normal development and homeostasis of multicellular organisms The process of apoptosis is controlled by a range of cell signaling pathways that originate either from cells external environment or from within the cell itself The cell’s fate to undergo apoptosis depends mainly on the dynamic balance between the Bcl-2 family sensor proteins which both promote and inhibit apoptosis In many (but not all) cases these proteins appear to influence the activation of caspase family members (proteases) which perform the ‘‘execution’’ phase of apoptosis by cleaving a number of cellular proteins and bringing about the destruction of cellular structures Apoptosis may be used by the host to limit the production of viruses or to disseminate them However viruses use the apoptosis process to produce sufficient virus progeny to facilitate virus release The megalocytiviruses belonging to family iridoviridae infect a wide range of tropical marine and freshwater fish including grouper gourami cichlid red sea bream angel fish sea bass and lamp eye causing similar diseases in each species The forms of cell death evoked by iridoviruses are continually being disclosed and they include typical apoptosis and non-apoptotic cell death However the signaling pathways involved in these processes remain largely unknown In this study i showed that GSIV encoded serine/threonine kinase gene induces apoptotic cell death via a p53-mediated upregulation of Bax which causes a loss of MMP Therefore we first time reported that the tumor suppressor protein p53 is involved to propagate the signal to commit suicide in fish cells This loss then mediates cell death signaling which results in an activation of the caspase-mediated cell death pathway at the mid-to-late stages of viral replication These findings may provide new insight into GSIV-induced pathogenesis In 2nd part of my study overexpression of Bcl-2 and Bcl-xL anti-apoptotic genes protect GF-1 cells from GSIV encoded serine/threonine kinase induced pro-apoptotic stimuli In this study i try to determine if these proteins could provide equal protection when challenged with a viral apoptotic gene Bcl-2 and Bcl-xL overexpression inhibit Bax oligomerization and mitochondrial outer membrane permeabilization Therefore we demonstrated that GSIV st-kinase induced cell death is prevented by the antiapoptotic Bcl-2 and Bcl-xL which enhances host cell viability through blockage of mitochondrial disruption and caspase 9 and caspase 3 activation These results indicate that Bcl-xL and Bcl-2 confer different ability to protect against GSIV serine/threonine kinase induced cell death which appears to be dependent on the molecular mechanism
Date of Award2017 Aug 18
Original languageEnglish
SupervisorHao-Ven Wang (Supervisor)

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