Thomas, Elaine Rhiannon; (2002) HIV-2 neutralisation: Interactions between viral glycoproteins and cell surface receptors. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Entry of HIV into target cells is the result of virus-cell fusion mediated by interactions between viral glycoproteins and cell surface receptors. Some HIV-2 strains can infect cells in the absence of the major receptor CD4, by direct interaction with a chemokine coreceptor, usually either CCR5 or CXCR4. ROD B is a highly CD4-independent variant of the prototype HIV-2 isolate ROD A. Investigation of neutralisation sensitivity of ROD A and ROD B to sera from HIV-2 infected individuals and to monoclonal antibodies showed ROD B is highly sensitive to neutralisation. CD4-dependent ROD A was relatively resistant to neutralisation. However, induction of ROD A infection of CD4 negative cells by soluble CD4 rendered the virus highly sensitive to neutralisation. Many clinically relevant primary isolates of HIV-2 are able to infect coreceptor positive cells in the absence of CD4. In contrast to the highly neutralisation resistant phenotype of primary isolates of HIV-1, primary isolates of HIV-2 were susceptible to neutralisation when utilising a CD4 independent route of infection. CD4-independent ROD B was also less sensitive to neutralisation when infecting some CD4 positive cells. Antibody binding to viral envelope is often a predictor of neutralization efficacy. Antibody binding to both monomeric and oligomeric envelope proteins of ROD A and ROD B assayed by several methods does not correlate with neutralisation sensitivity. However, further analysis of antibody binding to HIV-2 envelope using virion capture assays and Biacore technology did reveal subtle differences in antibody affinity that may contribute to the increased neutralisation sensitivity of CD4- independent ROD B. Therefore, both the affinity of the antibody for viral envelope and the use of cellular CD4 play a role in determining sensitivity to neutralisation.

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