The role of HIV gp120 in the disruption of the immune system.
ABSTRACT The existence of HIV positive individuals who do not appear to progress to disease, or do so only very slowly (LTNPs), strongly suggest that factors other than virus pathogenicity determine disease. The occurence of HIV infected chimpanzees that remain disease free and other African SIV infected primates where disease is apparently species specific underscores the importance of host factors [1,2]. We have examined the immune response of LTNP patients using a variety of techniques including intracellular cytokine FACscan, anchor PCR analysis of the T cell receptor and HLA typing of class II genes by DNA sequencing. Our results to date confirm that the development of disease is consistent with activation of a susceptible immune system, and that this could be due to the fact that HLA-like sequences of HIV may 'allo' activate the host immune response. In order to test this hypothesis further we have examined whether gp120 itself can bind and present specific peptides which may be capable of eliciting 'allo' activation responses in particular hosts.
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ABSTRACT: We have used the erosion of telomeric DNA as a measure of cellular division to study the replicative history of isolated T-lymphocyte subpopulations from a group of HIV-infected long-term survivors and age-matched healthy controls. In keeping with previous studies, we found that CD45RO+ (memory) T-cells showed greater telomere erosion than CD45RA+ (naive) T-cells. We did not, however, find any significant differences in the telomere lengths of isolated CD4+, CD8+, CD45RA+ or CD45RO+ T-cells between HIV-infected long-term survivors and age-matched controls. Further, we found no evidence of telomerase activation in T-cells from the HIV-infected groups to account for the lack of telomere erosion. Our data show no evidence, through telomere shortening, of clonal exhaustion or replicative senescence due to an increased rate of immune cell turnover in HIV-infected long-term survivors.HIV Medicine 04/2000; 1(2):116-22. · 3.16 Impact Factor
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ABSTRACT: The mechanisms by which HIV-1 induces chronic pathogenic immune activation associated with disease progression remain unclear despite many years of AIDS research. One proposal suggests that sequence and structural mimicry between gp120 and HLA may endow HIV with the capacity to arouse alloreactive and autoimmune responses within the susceptible host, fueling disease progression in a manner similar to graft-versus-host disease (GVHD). Both gp120 and HLA share a common functional interaction with CD4 but also demonstrate peptide binding properties. Here we report the conserved nature of this feature across HIV-1 envelopes, the crucial role of the HLA homologous C5 region for peptide interactions, and the elimination of this property through specific antibody targeting. Given that the C5 domain mimics a HLA activation domain and the reported clinical benefits associated with nonneutralizing antibodies against this region, targeting the C5 domain may have use as a therapeutic vaccine to protect against disease progression.AIDS research and human retroviruses 07/2008; 24(6):845-55. · 2.18 Impact Factor
- Advances in Cancer Research - ADVAN CANCER RES. 01/2008; 101:349-395.