Interaction between the ovine Bst-2 paralogs and sheep Betaretroviruses

Murphy, Lita (2012) Interaction between the ovine Bst-2 paralogs and sheep Betaretroviruses. PhD thesis, University of Glasgow.

Abstract

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.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: S Agriculture > SF Animal culture > SF600 Veterinary Medicine; Q Science > QR Microbiology > QR355 Virology; Q Science > Q Science (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Supervisor's Name: Palmarini, Professor Massimo
• Date of Award: 2012
• Depositing User: Miss Lita Murphy
• Unique ID: glathesis:2012-3113
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 31 Jan 2012
• Last Modified: 10 Dec 2012 14:04
• URI: https://theses.gla.ac.uk/id/eprint/3113