Varicella-Zoster Virus evasion of the Interferon immune response

Aaron Irving (2008). Varicella-Zoster Virus evasion of the Interferon immune response PhD Thesis, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, The University of Queensland.

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Author Aaron Irving
Thesis Title Varicella-Zoster Virus evasion of the Interferon immune response
School, Centre or Institute Diamantina Institute for Cancer, Immunology and Metabolic Medicine
Institution The University of Queensland
Publication date 2008-03
Thesis type PhD Thesis
Supervisor Nigel McMillan
Total pages 286
Total colour pages 34
Total black and white pages 252
Subjects 11 Medical and Health Sciences
Abstract/Summary Many viruses have evolved mechanisms to antagonize the interferon (IFN) system, targeting all the major components involved in receptor binding and signalling. Although a number of these viral proteins are homologous to cellular proteins involved in IFN downregulation (e.g., viral IFN regulatory factors [vIRFs]), many share little resemblance to known proteins. To determine the IFN-blocking properties of these proteins, functional assays are required. Here, we present a new and rapid functional screening method, based on the 2FTGH cell line, which is able to determine viral gene products that inhibit the IFN-alpha/Jak-Stat signalling pathway. Expression cloning of viral IFN-blocking genes into 2FTGH and consequent selection with IFN-alpha and 6-thioguanine result in the outgrowth of cells that are no longer responsive to IFN-alpha. We also demonstrate that selection occurs if members of the Jak-Stat signalling pathway are lost. To show the utility of our system, we have used a known suppressor of IFN signalling, the human papillomavirus (HPV) E7 gene. Expression of E7 causes the loss of ability of 2FTGH cells to respond to IFN-alpha treatment because of a functional disruption of the signalling pathway. This approach offers a new strategy for identifying novel viral genes or new functions of already described viral genes that have a role in IFN-alpha signalling inhibition.
Keyword interferon, virus, screening, system, varicella-zoster, orf63, vzv, ifn, 2ftgh, isg
Additional Notes Colour pages: 25-26,65,67-68,70,75-76,78-79,90,97,99,101,102,104-105,107-108,110-111,135,146-147,159-161,166,169-171,283-285

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Created: Wed, 21 Apr 2010, 08:57:05 EST by Mr Aaron Irving on behalf of Library - Information Access Service