Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Differential Gene Expression in HIV-Infected Individuals Following ART.

ABSTRACT: A paired analysis of peripheral blood mononuclear cells (PBMCs) isolated before and after antiretroviral therapy (ART) from a robust number of HIV-infected patients (N=36). Results identify a total of 4,157 DEGs following ART in HIV-infected participants and the transition from a period of active virus replication before ART to one of viral suppression This study evaluated PBMC gene expression in cells from 36 (4 dropped from analysis) recently HIV-infected individuals to identify differentially expressed genes following 48 weeks of ART

ORGANISM(S): Homo sapiens

SUBMITTER: Akul Singhania

PROVIDER: E-GEOD-44228 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Differential gene expression in HIV-infected individuals following ART.

Massanella Marta M Singhania Akul A Beliakova-Bethell Nadejda N Pier Rose R Lada Steven M SM White Cory H CH Pérez-Santiago Josué J Blanco Julià J Richman Douglas D DD Little Susan J SJ Woelk Christopher H CH

Antiviral research 20130806 2

Previous studies of the effect of ART on gene expression in HIV-infected individuals have identified small numbers of modulated genes. Since these studies were underpowered or cross-sectional in design, a paired analysis of peripheral blood mononuclear cells (PBMCs), isolated before and after ART, from a robust number of HIV-infected patients (N=32) was performed. Gene expression was assayed by microarray and 4157 differentially expressed genes (DEGs) were identified following ART using multivar ...[more]

PMID: 23933117

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Project description:Background. HIV-infected individuals on antiretroviral therapy (HIV/ART) experience higher levels of non-AIDS morbidity than uninfected people, which is believed to be driven by inflammation that persists despite viral suppression. Elevations in plasma cytokines, coagulation markers and both innate and adaptive immune cell activation during untreated infection are often incompletely reversed by ART and associated with these morbidities. Monocytes/macrophages play a central role in many of these complications including neurocognitive and cardiovascular disease. Results. We investigated monocyte surface markers, gene expression and plasma cytokines in 11 HIV-infected older individuals (median age 53 years) who started therapy with low CD4 counts (median 129 cells/ul), with elevated hsCRP (≥2mg/L) despite long-term ART (median 7.4 years), along with age, gender, race and smoking status-matched controls. Major monocyte subsets (based on CD14/CD16/CD163) were not different from controls, but surface levels differed for CD163 (p=0.022), PD1 (p=0.015) and a trend for tissue factor (p=0.098). As a group, HIV/ART subjects had elevated levels of plasma CCL2 (MCP-1; p=0.0001), CXCL9 (MIG; p=0.04) and sIL2R (p=0.015), which were highly correlated, whereas sCD14 and several other markers were not significantly elevated. However, principal component analysis of soluble markers revealed that about half of HIV/ART subjects clustered with controls, whereas the remainder were distinct, driven by IL-10, CCL11, CXCL10, CXCL11 as well as CCL2, CXCL9 and sIL2R. Outlier subjects were significantly older than those who clustered with controls. Gene expression analysis unexpectedly revealed downregulation in HIV/ART monocytes of multiple genes linked to immune functions including inflammation, immune cell development and cell-cell signaling. Conclusions. These results reveal a novel pattern of immune dysregulation involving both aberrant inflammation and monocyte dysfunction, which suggests complex mechanisms linking monocytes and HIV/ART comorbidities.

Dataset Information

Differential Gene Expression in HIV-Infected Individuals Following ART.

Publications

Differential gene expression in HIV-infected individuals following ART.

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