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Title: vOX2 - a potential immune regulatory protein involved in Kaposi's sarcoma-associated herpesvirus pathogenesis
Author: Brass, Amanda Francine
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2004
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Studies on the viral gene, vOX2, have indicated that this 55kDa glycoprotein has a similar structure to the human CD200, an immunoglobulin superfamily gene, containing two extracellular domains, a single transmembrane region and a short cytoplasmic tail. In order to investigate the potential role of vOX2 in an in vivo system, a novel murid herpesvirus, murine herpesvirus 76 (MHV-76), was utilised. MHV-76 is a natural deletion mutant of murine herpesvirus 68 (MHV-68), lacking four unique genes and eight viral tRNA-like genes from the left end of the MHV-68 genome. This deletion has provided an opportunity to generate a recombinant MW-76 virus expressing vOX2 (MHV76-vOX2) and a selection marker (GFP-HygR), thus allowing a functional study of vOX2 through the infection of mice. A control recombinant virus (MHV76-IRES) was also generated, which only expressed the selection marker (GFP-HygR). The genomic structures of all recombinant viruses were verified by Southern blot analysis and the expression of the inserted genes was confirmed by Northern blot analysis. The growth kinetics of MHV76-vOX2 and MHV76-IRES were compared with wild type MHV-76 in both an in vitro single-step and multi-step growth assay. The growth kinetics of the recombinant viruses was not significantly different from that of MHV-76. In vivo studies have indicated that vOX2 has an effect on viral replication; a 10 to 100 fold increase in viral lung titres was observed in mice infected with MHV76-vOX2 compared to the control recombinant virus. Examination of lung sections showed that mice infected with the vOX2 recombinant virus elicited a strong influx of inflammatory cells, particularly peripheral mononucleocytes (PMN) and macrophages, resulting in perivascular and peribronchiolar inflammation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available