title: Gene expression profile in long-term non progressor HIV infected patients: in search of potential resistance factors.
abstract: Long-term non-progressors (LTNP) represent a minority (1-5%) of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm(3) and low viremia in the absence of antiretroviral treatment. Protective factors described so far such as the CCR5delta32 deletion, protective HLA alleles, or defective viruses fail to fully explain the partial protection phenotype. The existence of additional host resistance mechanisms in LTNP patients was investigated here using a whole human genome microarray study comparing gene expression profiles of unstimulated peripheral blood mononuclear cells from LTNP patients, HIV-1 infected patients under antiretroviral therapy with CD4+ T cell levels above 500/mm(3) (ST), as well as healthy individuals. Genes that were up- or downregulated exclusively in LTNP, ST or in both groups in comparison to controls were identified and classified in functional categories using Ingenuity Pathway Analysis. ST and LTNP patient groups revealed distinct genetic profiles, regarding gene number in each category and up- or downregulation of specific genes, which could have a bearing on the outcome of each group. We selected some relevant genes to validate the differential expression using quantitative real-time qRT-PCR. Among others, we found several genes related to the canonical Wnt/beta-catenin signaling pathway. Our results identify new possible host genes and molecules that could be involved in the mechanisms leading to the slower progression to AIDS and sustained CD4+ T cell counts that is peculiar to LTNP patients.
authors: Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology, INCT, São Paulo, Brazil.
authors: Maria Carolina
authors: MC
authors: Luque
authors: Heart Institute (Incor) - HCFMUSP, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Camila C
authors: CC
authors: Santos
authors: Heart Institute (Incor) - HCFMUSP, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, INCT, São Paulo, Brazil.
authors: Eliane C
authors: EC
authors: Mairena
authors: Collaborative Genomics Center, Vaccine and Gene Therapy Institute, Port Saint Lucie, FL, USA.
authors: Peter
authors: P
authors: Wilkinson
authors: Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Canada.
authors: Genèvieve
authors: G
authors: Boucher
authors: Department of Infectious Diseases, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Aluisio C
authors: AC
authors: Segurado
authors: Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo, São Paulo, Brazil.
authors: Luiz A
authors: LA
authors: Fonseca
authors: Department of Infectious Diseases, University of São Paulo School of Medicine, São Paulo, Brazil.
authors: Ester
authors: E
authors: Sabino
authors: Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo, São Paulo, Brazil; Heart Institute (Incor) - HCFMUSP, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, INCT, São Paulo, Brazil.
authors: Jorge E
authors: JE
authors: Kalil
authors: Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo, São Paulo, Brazil; Heart Institute (Incor) - HCFMUSP, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, INCT, São Paulo, Brazil. Electronic address: edecunha@usp.br.
authors: Edecio
authors: E
authors: Cunha-Neto
mesh_terms: D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016022:Case-Control Studies; D018450:Disease Progression; D060467:Disease Resistance / Q000235:genetics*; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D059467:Transcriptome; D019562:Viral Load
keywords: CD4+ T cells; Cell survival; Gene expression profiling; HIV; Long-term nonprogressors