Gene expression profile in long-term non progressor HIV infected patients: In search of potential resistance factors

• Published in: Molecular immunology Vol. 62; no. 1; pp. 63 - 70
• Main Authors: Luque, Maria Carolina, Santos, Camila C., Mairena, Eliane C., Wilkinson, Peter, Boucher, Genèvieve, Segurado, Aluisio C., Fonseca, Luiz A., Sabino, Ester, Kalil, Jorge E., Cunha-Neto, Edecio
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2014
• Subjects: Case-Control Studies; CD4 Lymphocyte Count; CD4+ T cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Cell survival; Disease Progression; Disease Resistance - genetics; Female; Gene expression profiling; HIV; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV Long-Term Survivors; HIV-1 - immunology; Humans; Long-term nonprogressors; Male; Microarray Analysis; Transcriptome; Viral Load; Cell survival; CD4+ T cells; HIV; Gene expression profiling; Long-term nonprogressors
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2014.05.016

•HIV+ LTNP patients take more than 10 years to progress to AIDS.•HIV+ LTNP have normal CD4+ T cell counts.•PBMC of HIV+ LTNP display an antiapoptotic, pro-T cell survival gene expression profile.•PBMC of HIV+ LTNP display activation of the WNT-β-catenin pathway validated by qPCR.•CD4+ T cells of HIV+ LTNP might survive due to the observed gene expression profile. 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/mm3 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/mm3 (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.