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Title: Characterisation of HIV-1 Cell-to-Cell Transfer across the Virological Synapse.
Author: Mitar, Ivonne Maria
ISNI:       0000 0001 3411 2172
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2007
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HIV-1 is believed to spread by two mechanisms in an infected host: by cell-free virions and by cell-associated transmission. The mechanisms of HIV-1 cell-to-cell transmission were not well understood until the recent description of the virological synapse (VS). The VS is a specialised supramolecular structure, formed between an infected effector cell and a permissive target cell, to facilitate direct virus infection of the permissive cell. Direct cell-to-cell spread is probably an important mechanism in tissues densely populated with target cells, such as CD4+ T cells in lymph nodes and the GALT. Moreover, VS-mediated viral transfer may help the virus to 'hide' from elements of the immune system, such as neutralising antibodies and complement. Many areas relating to HIV-1 cell-to-cell spread and VS function remain to be explored. Therefore, the aim of the project behind this thesis was to extend our initial molecular characterisation of the supramolecular structure of VS in T cells and to identify viral and cellular key players involved in VS-dependent HIV-1 cell-tocell spread. In this thesis I have characterised the dynamics of VS formation by live cell imaging, quantified cell-to-cell spread kinetics and shown that HIV-1 cell-to-cell spread is more efficient than cell-free virion spread. Further I have demonstrated the involvement of host cytoskeleton components and cognate adhesion molecule interactions in the process of VS formation and cell-to-cell spread. Finally, I present preliminary data on the R5 virUS-dependent VS and show that CCR5-using viruses are capable of forming supramolecular VS analogous to that observed with CXCR4using HIV-1. Further deciphering of the underlying molecular mechanisms of VS formation will doubtless contribute to our understanding of viral pathogenesis and viral immune evasion, and have implications in future therapeutic interventions.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available