Navegando por Palavras-chave "sobreviventes de longo prazo ao hiv"

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    Rede transcricional da resposta do hospedeiro à infecção pelo HIV-1
    (Universidade Federal de São Paulo (UNIFESP), 2014-12-19) Zanoni, Michelle [UNIFESP]; Diaz, Ricardo Sobhie Diaz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Host transcriptional network response to HIV-1 infection In this study we investigated 84 transcription network genes in peripheral blood mononuclear cells from 10 antiretroviral naïve individuals experiencing distinct pace of HIV disease progression, and 10 individuals experiencing distinct CD4+ T cells recovery after HAART; all patients belonging to the city of Sao Paulo recent HIV infection Cohort. Investigated genes relate to mechanisms associated to HIV-1 infection susceptibility, natural viral replication control, disease progression rate and immune reconstitution. We evaluated four representative groups of individuals at two distinct time points: antiretroviral naïve elite controllers and rapid progressors evaluated during recent HIV infection period and 1 year after; and immunological responders versus immunological non-responders before HAART initiation and 1 year after. Enhanced dendritic cells cross-presentation to antigen-specific CD8+ T cells evidenced by XCL1 gene upregulation combined with immune activation control (CD4 down-regulation) correlated with natural viremia control during recent infection. In contrast, rapid progressors presented up-regulation of innate immune component (IFNG) added by up-regulation of genes involved in virus transcription activation (CDK9, CCNT1, EP300 and CEBPB) together with remarkable pro-apoptosis signaling (CASP3, TRAIL and TNRF2 and BCL2 lacking) observed 1 year after diagnosis. On the other hand, successfully CD4+ T cell recovery predictors before HAART intervention correlated with ELANE and SLPI upregulation possibly associated to periphery myeloid progenitor cells mobilization and hematopoiesis driven mechanisms added to CD44 up-regulation 1 year after HAART suggesting lymphopoiesis, hematopoieses and CD4+ T cells being driven to Peyer patches. Compared to uninfected controls, immunological non-responders presented 30% of genes differentially expressed (P<0.05) 1 year after HAART, with exception of CD4, CCR4 and RBL2 down-regulation, most of observed transcripts were up-regulated. Lack of satisfactory immune response after HAART also correlated to TGFB1, IL10, STAT3, CEBPB and TNFR2 genes, a scenario probably related to regulatory T cells combined to additional inhibitory effects on dendritic cells maturation status (DCSIGN) associated to sustained chronic innate immune activation (IFNA) with immune senescence and persistence of virus transcription activation (CDK9, CCNT1 and CEBPB). Therefore, the host transcriptional network response to HIV-1 infection described here emerging during early stages of HIV infection or during the course of infection, and before/after HAART initiation can be considered as tools to provide insights into the knowledge of pathogenic mechanisms. Furthermore, these results enables us to develop biomarker tools for disease progression prediction or immune reconstitution after HAART, as well as helping in the development of immune therapies and other interventions that could potentially enable patients to better respond to HIV and HIV treatment.