AI Article Synopsis
- LTNP individuals comprise a small percentage (1-5%) of HIV-infected people who maintain stable immune health without antiretroviral therapy for over 7-10 years, characterized by high CD4+ T cell counts and low virus levels.
- Previous protective factors such as specific gene deletions and alleles do not completely explain why some LTNPs resist disease progression, prompting further investigation into other genetic factors.
- A gene expression study comparing LTNPs, treated HIV patients, and healthy individuals revealed distinct genetic profiles, leading to the identification of new genes that may contribute to LTNPs' slower progression to AIDS and better immune health.
Article 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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| http://dx.doi.org/10.1016/j.molimm.2014.05.016 | DOI Listing |
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