May, Jacqueline Carol; (1998) The role of envelope glycoprotein in human immunodeficiency virus type 2 disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Progression to AIDS following HIV-2 infection is generally slower than for HIV-1, however, rapid progression has been observed in some HIV-2 infected individuals. This disparity between HIV-1 and HIV-2 infection may be due to either HIV-2 having an attenuated viral phenotype or, alternatively, enhanced immunological control of HIV-2 replication, which may prolong the asymptomatic phase of disease. The envelope glycoprotein of HIV contributes to both of these phenomena; it contains regions that determine viral phenotype and is also a major target for host immunological responses. This thesis describes the development of a highly efficient plasmid vector for the PCR cloning and eukaryotic expression of recombinant envelope glycoproteins, together with an ELISA to measure the properties of these glycoproteins. These techniques have enabled us to perform quantification and functional analyses of various HIV-2 env glycoproteins (rgp105) and to examine their function, antigenicity and role in determining disease progression rate. Significant diversity in antigenicity and CD4 binding was found between clones derived from single isolates, between different isolates and between patients. However, we found no strong correlation between rgp105-CD4 affinity and viral phenotype or patient clinical status. Analysis of humoral responses to whole HIV-2 antigens and to rgp105 showed no difference between progressing and non-progressing patients. In contrast, fine mapping of the HIV-2 envelope using a panel of 210 overlapping 12mer oligopeptides identified two peptides within the gp36 transmembrane domain which were differentially recognised. Further investigation showed that humoral responses to amino acids 645-656 were significantly elevated in patients with better disease prognosis. Therefore, host humoral responses may play an important role in protecting the host from disease and in extending the clinically asymptomatic phase of HIV-2 infection. These findings maybe important in the development of preventive or prophylactic vaccines for the treatment of both HIV-1 and HIV-2 infections.

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