Meta-analysis of gene expression profiles in long-term non-progressors infected with HIV-1.
BMC Med Genomics
; 12(1): 3, 2019 01 09.
Article
em En
| MEDLINE
| ID: mdl-30626383
ABSTRACT
BACKGROUND:
In the absence of antiretroviral treatments (ARTs), a small group of individuals infected with HIV, including long-term non-progressors (LTNPs) who maintain high levels of CD4+ T cells for more than 7-10 years in the absence of ART and in particular a subgroup of LTNPs, elite controllers (ECs), who have low levels of viremia, remain clinically and/or immunologically stable for years. However, the mechanism of stable disease progression in LTNPs and ECs needs to be elucidated to help those infected with HIV-1 remain healthy. In this study, to identify the characteristics of gene expression profiles and biomarkers in LTNPs, we performed a meta-analysis using multiple gene expression profiles among LTNPs, individuals infected with HIV-1 without ART, individuals infected with HIV-1 with ART, and healthy controls.METHODS:
The gene expression profiles obtained from the Gene Expression Omnibus (GEO) microarray data repositories were classified into three groups LTNPs versus healthy controls (first group, 3 studies), LTNPs versus patients infected with HIV-1 without ART (second group, 3 studies), and LTNPs versus patients infected with HIV-1 with ART (third group, 3 studies). In addition, we considered a fourth group, patients infected with HIV-1 without ART versus healthy controls (3 studies), to exclude genes associated with HIV-1 infection in the three groups. For each group, we performed a meta-analysis using the RankProd method to identify and compare the differentially expressed genes (DEGs) in the three groups.RESULTS:
We identified the 14 common DEGs in the three groups when comparing them with each other. Most belonged to immune responses, antigen processing and presentation, the interferon-gamma-mediated signaling pathway, and T cell co-stimulation. Of these DEGs, PHLDA1 was up-regulated and ACTB and ACTG1 were down-regulated in all three groups. However, the rest of the up- or down-regulated genes were discordant in the three groups. Additionally, ACTB and ACTG1 are known to inhibit viral assembly and production, and THBS1 is known to inhibit HIV-1 infection.CONCLUSIONS:
These results suggest that significant genes identified in a meta-analysis provide clues to the cause of delayed disease progression and give a deeper understanding of HIV pathogenesis in LTNPs.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Perfilação da Expressão Gênica
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
BMC Med Genomics
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2019
Tipo de documento:
Article