Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597615
Title: Natural killer cell recognition of virally infected cells
Author: Chisholm, S. E.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2005
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Abstract:
Natural killer (NK) cells are known to be important for the control of viral infections, particularly infection with large double stranded (ds)DNA viruses such as herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV), but the pathways and interactions important for NK cell recognition of virally infected cells are not well understood. Thus, the aim of this thesis was to study the molecular mechanisms of NK cell recognition of target cells infected with either HSV-1 or VV. Experiments using a set of HSV-1 mutants, deficient in one or more of the immediate early (IE) genes, demonstrated that expression of ICP0 alone was found to be sufficient to render HSV-1 infected target cells susceptible to NK attack, and killing assays demonstrated that the natural cytotoxicity receptors (NCRs) were involved in the NK mediated killing of HSV-1 infected targets. For VV, it was not possible to narrow down exactly which VV gene was sufficient for generating NK cell mediated susceptibility, but the data indicated that the VV gene or genes involved are expressed early, conserved within the poxvirus family, and as such, likely to be essential for the virus. Flow cytometry experiments demonstrated that altered susceptibility of the target cells to NK cell lysis was due to upregulation of ligands for the NCRs, and the importance of the NCRs in NK mediated killing of VV infected targets was confirmed by killing assays. In addition, flow cytometry experiments demonstrated very little down regulation of MHC class I followed infection by either HSV-1 or VV, implying that MHC class I down regulation is not of major importance in NK mediated killing of infected cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.597615  DOI: Not available
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