There is a delicate evolutionary balance between viruses and their hosts. The host has evolved the intrinsic, innate and adaptive immunity to fight viral infections. However, viruses have acquired several counteracting measures to evade host defences. Ovine Betaretroviruses, including the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV) and the highly related endogenous enJSRVs are a unique model system to investigate virus-host interaction over long evolutionary periods. Sheep have co-opted some defective enJSRV loci to (i) counteract infection by exogenous viruses and likely (ii) to cope with the continuous retroviral invasion of their genome. In addition, various genes of the innate and intrinsic immunity of the host have evolved to block viral replication. The work presented in this thesis focuses on the ovine bone marrow stromal cell antigen 2 (Bst-2)/ tetherin, a recently identified cellular restriction factor with a broad antiviral activity, and its interaction with sheep Betaretroviruses. In sheep, the BST-2 gene is duplicated into two paralogs termed oBST-2A and -2B. Studies presented in this thesis show that oBST-2B possesses several biological properties distinct from the paralog oBST-2A and from all the other BST-2 orthologs. oBST-2A prevents the release of JSRV/enJSRV viral particles by ‘tethering’ them at the cell membrane similarly to what observed by human BST-2. On the other hand, oBST-2B, does not reach the cell membrane but remains within the Golgi stacks and the trans-Golgi network. Several lines of evidence obtained in this thesis suggest that oBST-2B reduces significantly Env incorporation into viral particles. Therefore, oBST-2B possesses a unique antiviral activity that complements the classical tethering restriction provided by oBST-2A.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:547210 |
| Date | January 2012 |
| Creators | Murphy, Lita |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/3113/ |
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