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Available from: Darren P Martin, Dec 12, 2013
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    ABSTRACT: Some HIV infected individuals remain asymptomatic for protracted periods of time in the absence of antiretroviral therapy (ART). Virological control, CD4 T cell loss and HIV-specific responses are some of the key interrelated determinants of HIV-1 disease progression. In this study, possible interactions between viral load, CD4 T cell slopes, host genetics and HIV-specific IFN-gamma responses were evaluated in chronically HIV-1-infected adults. Multilevel regression modeling was used to stratify clade A or D HIV-infected individuals into disease progression groups based on CD4 T cell slopes. ELISpot assays were used to quantify the frequency and magnitude of HIV-induced IFN-gamma responses in 7 defined rapid progressors (RPs) and 14 defined slow progressors (SPs) at a single time point. HLA typing was performed using reference strand conformational analysis (RSCA). Although neither the breadth nor the magnitude of the proteome-wide HIV-specific IFN-gamma response correlated with viral load, slow disease progression was associated with over-representation of host immunogenetic protective HLA B* alleles (10 of 14 SPs compared to 0 of 7; p = 0.004, Fisher's Exact) especially B*57 and B*5801, multiclade Gag T-cell targeting (71%, 10 of 14 SPs compared to 14%, 1 of 7 RPs); p = 0.029, Fisher's Exact test and evident virological control (3.65 compared to 5.46 log10 copies/mL in SPs and RPs respectively); p<0.001, unpaired student's t-test These data are consistent with others that associated protection from HIV disease with inherent host HLA B allele-mediated ability to induce broader Gag T-cell targeting coupled with apparent virological control. These immunogenetic features of Gag-specific immune response which could influence disease progression may provide useful insight in future HIV vaccine design.
    PLoS ONE 01/2009; 4(1):e4188. DOI:10.1371/journal.pone.0004188 · 3.53 Impact Factor
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    ABSTRACT: HLA class I allele types have differential impacts on the level of the pVL and outcome of HIV-1 infection. While accumulations of CTL escape mutations at population levels have been reported, their actual impact on the level of the pVL remains unknown. In this study HLA class I types from 141 untreated, chronically HIV-1 infected Japanese patients diagnosed from 1995-2007 were determined, and the associations between expression of individual HLA alleles and level of pVL analyzed. It was found that the Japanese population has an extremely narrow HLA distribution compared to other ethnic groups, which may facilitate accumulation of CTL escape mutations at the population level. Moreover while they uniquely lack the most protective HLA-B27/B57, they commonly express the alleles that are protective in Caucasians (A11:10.4%, A26:11.55%, B51:8.6% and Cw14:12.7%). Cross-sectional analyses revealed no significant associations between expression of individual alleles and the level of the pVL. The patients were then stratified by the date of HIV diagnosis and the analyses repeated. It was found that, before 2001, B51+ individuals displayed significantly lower pVL than the other patients (median: 5150 vs. 18,000 RNA copies/ml, P=0.048); however thereafter this protective effect waned and disappeared, whereas no changes were observed for any other alleles over time. These results indicate that, at a population level, some HLA alleles have been losing their beneficial effects against HIV disease progression over time, thereby possibly posing a significant challenge for HIV vaccine development. However such detrimental effects may be limited to particular HLA class I alleles.
    Microbiology and Immunology 04/2010; 54(4):196-205. DOI:10.1111/j.1348-0421.2010.00206.x · 1.31 Impact Factor
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    ABSTRACT: The swine major histocompatibility complex (MHC) or swine leukocyte antigen (SLA) complex is one of the most gene-dense regions in the swine genome. It consists of three major gene clusters, the SLA class I, class III and class II regions, that span ∼1.1, 0.7 and 0.5 Mb, respectively, making the swine MHC the smallest among mammalian MHC so far examined and the only one known to span the centromere. This review summarizes recent updates to the Immuno Polymorphism Database-MHC (IPD-MHC) website (http://www.ebi.ac.uk/ipd/mhc/sla/) which serves as the repository for maintaining a list of all SLA recognized genes and their allelic sequences. It reviews the expression of SLA proteins on cell subsets and their role in antigen presentation and regulating immune responses. It concludes by discussing the role of SLA genes in swine models of transplantation, xenotransplantation, cancer and allergy and in swine production traits and responses to infectious disease and vaccines.
    Developmental and comparative immunology 03/2009; DOI:10.1016/j.dci.2008.07.002 · 3.71 Impact Factor