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

Authors
  • Luque, Maria Carolina1
  • Santos, Camila C2
  • Mairena, Eliane C3
  • Wilkinson, Peter4
  • Boucher, Genèvieve5
  • Segurado, Aluisio C6
  • Fonseca, Luiz A7
  • Sabino, Ester6
  • Kalil, Jorge E8
  • Cunha-Neto, Edecio9
  • 1 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. , (Brazil)
  • 2 Heart Institute (Incor) - HCFMUSP, University of São Paulo School of Medicine, São Paulo, Brazil. , (Brazil)
  • 3 Heart Institute (Incor) - HCFMUSP, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology, INCT, São Paulo, Brazil. , (Brazil)
  • 4 Collaborative Genomics Center, Vaccine and Gene Therapy Institute, Port Saint Lucie, FL, USA.
  • 5 Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Canada. , (Canada)
  • 6 Department of Infectious Diseases, University of São Paulo School of Medicine, São Paulo, Brazil. , (Brazil)
  • 7 Division of Clinical Immunology and Allergy, Department of Medicine, University of São Paulo, São Paulo, Brazil. , (Brazil)
  • 8 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. , (Brazil)
  • 9 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: [email protected] , (Brazil)
Type
Published Article
Journal
Molecular immunology
Publication Date
November 2014
Volume
62
Issue
1
Pages
63–70
Identifiers
DOI: 10.1016/j.molimm.2014.05.016
PMID: 24967879
Source
Medline
Keywords
License
Unknown

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.

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