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Title: Molecular and functional analysis of human immunodeficiency virus type 1 ENV genes
Author: Ashelford, Sarah
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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The principal target of antibodies that can neutralise HIV-1 infection in vitro is the surface envelope protein, encoded by the envelope gene (env). The env gene evolves rapidly during the course of infection, producing a multitude of variants, many of which show different sensitivities to neutralisation by antibodies. The work described in this thesis, examines the hypothesis that the selection of antibody-resistant variants of the env gene is a strong force shaping the evolution of the env gene, a process that allows the virus to persist in the face of a strong immune response. In order to examine the antibody-response to the env gene, 19 HIV-1 clones were constructed by replacing the env gene of the infectious molecular clone pHXB2-D, with homologous env sequences obtained from a single individual. The 19 env genes were obtained directly from patient peripheral blood mononuclear cell DNA using the polymerase chain reaction. The sequences of the env genes represent the predominant types found in the plasma at seroconversion and in five subsequent years of infection within this individual. No inactivating mutations were found following the partial sequencing of each env clone. Following the introduction of the recombinant proviral clones into human T-cell cultures, only five of the 19 showed evidence of the production of high-replicating viruses. Viruses from these clones induced cell-to-cell fusion (or syncytia), and were capable of growth in a variety of human T-cell lines. With the remaining 14 clones, three showed evidence of low level replication in human peripheral blood mononuclear cells, but failed to replicate in T-cell lines and did not induce the formation of syncytia. The remaining 11 clones but did not show evidence of productive infection. In conclusion, despite being taken directly from an infected patient, only a small proportion of env genes were found to support productive infection in vitro.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available