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Title: The role of specific MHV-68 genes in persistent infection in the lung and virus pathogenesis
Author: Templeton, Kerra Marianne
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2006
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Murine gamma herpesvirus-68 (MHV-68) is able to undergo lytic replication in a range of cell types in vitro and can infect inbred strains of mice. These properties make MHV-68 an excellent model for the study of gammaherpesvirus pathogenesis. MHV-68 allows investigation of gammaherpesvirus infection of and persistence in the lung – following intranasal inoculation the virus establishes a life-long infection in this organ, with virus persisting in epithelial cells and/or B cells. Identification of key viral genes required for persistence may allow for development of vaccination and/or treatment strategies. Using real-time PCR the long-term viral load in the lungs was reduced following the deletion of key genes from the viral genome. Genes identified are the Thymidine kinase gene, previously shown to play a role during acute infection of the lung and ORF73, a homologue of the HSKV LANA-1 gene. Initial data also suggests that the ORF72 and M11 genes, both involved in reactivation from latency, may play a role in maintaining viral load at late time points post-infection. In vivo investigation of the M1 gene of MHV-68 has demonstrated a potential role in control of viral reactivation from latency in the spleen. A novel MHV-68 mutant, M1Δ, lacking 1171 bp of the M1 ORF, was used to study the role of M1 in pathogenesis. Initial data suggests that in vivo infection with M1Δ results in increased viral titres during acute infection of the lung, indicating a potential role in control of initial infection. The major role of M1 appears to be during acute phase latency in the spleen.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available