The principal target of antibodies that can neutralise HIV-1 infection <I>in vitro</I> is the surface envelope protein, encoded by the envelope gene (<I>env</I>). The <I>env</I> 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 <I>env </I>gene is a strong force shaping the evolution of the <I>env</I> 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 <I>env</I> gene, 19 HIV-1 clones were constructed by replacing the <I>env</I> gene of the infectious molecular clone pHXB2-D, with homologous <I>env</I> sequences obtained from a single individual. The 19 <I>env</I> genes were obtained directly from patient peripheral blood mononuclear cell DNA using the polymerase chain reaction. The sequences of the <I>env</I> 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 <I>env</I> 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 <I>env</I> genes were found to support productive infection <I>in vitro. </I>
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:641102 |
| Date | January 1996 |
| Creators | Ashelford, Sarah |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/11565 |
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