Use this URL to cite or link to this record in EThOS:
Title: Interaction of HTLV-1 with soluble and cell surface polyanions
Author: Römer, Daniela
ISNI:       0000 0001 3539 1214
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2008
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
The Human T-cell lymphotropic virus type-l (HTLV-I) is a retrovirus infecting 10-20 million people worldwide. It causes fatal adult T cell leukaemia/lymphoma and the neurological inflammatory disease HAM/TSP in a percentage of infected individuals. The virus is transmitted within and between individuals by HTLV-I infected T lymphocytes. Transmission between individuals occurs via breastfeeding, intravenous blood transfusion or sexually. Intercellular transmission is thought to occur by the formation of a virological synapse. Previous work in my laboratory had demonstrated that HTLV-1 interacts with both cell surface heparan sulphate proteoglycans (HSPGs) and soluble polyanionic molecules via the viral envelope surface glycoprotein gp46. In this thesis, I first investigated whether synthetic soluble polyanions, developed as topical candidate microbicides for inhibition ofHIV-1 sexual transmission, had p.otential to inhibit HTLV-I infection. Using a variety of in vitro assays I demonstrated that the polyanions PRO 2000, Dextran sulphate (DexS) and Dextrin-2-sulphate (D2S) inhibi t HTLV-1 infectivity to varying degrees. I also demonstrated that a peptide inhibitor of HTLV-1 fusion was active at inhibiting viral spread, and moreover that this peptide synergised with soluble polyanions in its antiviral activity. My second area of research was based upon another observation made previously, that HTLV-I-transformed cell lines expressed very high levels of HSPGs, cell surface molecules involved in cell homing and cell-cell communication. My working hypothesis was that HTLV-1 infection, or HTLV-1 Tax alone, may upregulate HSPGs in order to increase viral spread. However, using a range of assays including chronically HTLV-I-infected T cells, ex vivo patient T cells and Tax-transfected primary T cells, I disproved this hypothesis. I concluded that HSPG upregulation was independent of HTLV-1 infection and Tax expression, but depended on culture conditions and cell activation state. Moreover, abundant HSPG expression on stably transfected target cells did not influence HTLV-I cellcell spread.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available