title: Uniquely altered transcripts are associated with immune preservation in HIV infection.
abstract: The mechanisms underlying host HIV control hold much promise in the search for a functional HIV cure. We investigated the host genomic signatures in elite controllers or rapid progressors following recent infection and the correlates of immune reconstitution during combination antiretroviral therapy. We characterized the HIV-specific longitudinal host transcriptional response of peripheral blood mononuclear cells from elite controllers, rapid progressors, immune responders and non-responders using a RT-qPCR array in a cohort of recently HIV-infected Brazilian individuals. The elite controllers expressed unique transcripts early in infection that were closely associated with specialized cross-presentation between XCR1+ DCs and antigen-specific CD8+ T cells (XCL1). The natural suppression of HIV was also associated with the highly functional co-expression of cytokines and chemokines (CCL2, TNF and IL-10) concomitant with the maintenance of important anti-inflammatory and anticoagulant properties (Antithrombin III). Immune responders exhibited exclusively upregulated mRNAs possibly related to stem cell mobilization before combination antiretroviral therapy (neutrophil elastase). Our longitudinal approach to gene expression permitted us to discover previously unrecognized determinants that contribute to natural or antiretroviral-mediated HIV-1 immune control.
authors.affiliation: Retrovirology Laboratory, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Michelle
authors.initials: M
authors.lastname: Zanoni
authors.affiliation: Retrovirology Laboratory, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ítalo Karmann
authors.initials: ÍK
authors.lastname: Aventurato
authors.affiliation: Retrovirology Laboratory, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: James
authors.initials: J
authors.lastname: Hunter
authors.affiliation: Retrovirology Laboratory, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Maria Cecilia Araripe
authors.initials: MC
authors.lastname: Sucupira
authors.affiliation: Retrovirology Laboratory, Department of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ricardo Sobhie
authors.initials: RS
authors.lastname: Diaz
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D000990:Antithrombin III / Q000235:genetics / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use; D001938:Brazil; D018791:CD4 Lymphocyte Count; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D018925:Chemokines; D016207:Cytokines; D015235:HLA-B Antigens; D000990:Antithrombin III