Transcriptomics,Genomics

Dataset Information

19

IFN-a-induced monocyte phenotype in chronic unsuppressed HIV infection


ABSTRACT: Abstract Objectives: HIV infection dysregulates the innate immune system and alters leukocyte gene expression. The objectives were two fold: to characterize the impact of HIV infection on peripheral monocyte gene expression and to identify the predominant factor(s) responsible for altered gene expression. Design and methods: In a cross-sectional study, CD14+ monocytes were isolated from 11 HIV seronegative controls, 22 HIV seropositive subjects with low viral loads (LVL, <= 10,000 RNA copies/ml) and 22 HIV seropositive subjects with high viral loads (HVL, > 10,000 RNA/copies/ml). Total monocyte RNA was hybridized to 55K probes on high-density microarrays to obtained detailed gene expression profiles from control, LVL and HVL subjects. As potential candidates for immune disruption, we evaluated three HIV-related peripheral factors, interferon (IFN)-a, IFN-a and lipopolysaccharide (LPS) by treating HIV seronegative CD14+ monocytes for 48h and then analyzing gene expression. Plasma collected from the HIV subjects were quantified for LPS using a Pyrogene assay and for soluble (s) CD14 by ELISA. Results: In this cross-sectional study of HIV subjects (n=44), viral loads above 10,000 RNA copies/ml were associated with an activated phenotype. Characterization of the gene expression pattern by Gene Ontology reveals an ongoing immune response to viral infection including inflammation and chemotaxis. Gene expression analysis of in vitro treated HIV seronegative monocytes with IFN-a, IFN-g or LPS demonstrated that IFN-a most accurately recapitulated the HIV HVL profile. There was no detectable LPS signature even in those HIV subjects with the highest LPS and sCD14 levels. Conclusions: Monocyte gene expression in subjects with viremia is predominantly due to IFN-a, while subjects with LVL have a non-activated phenotype. In monocytes, there was no discernible expression profile linked to LPS exposure. Overall design: Global gene expression analysis using high-density cDNA microarrays was performed on CD 14+ monocytes isolated from 55 subjects, 22 with HIV HVL, 22 with HIV LVL and 11 HIV seronegative controls. The categorization of high or low viral load was based on clinical criteria with LVL <10,000 RNA copies/ml and HVL as >10,000 RNA copies/ml. Subjects in the study were males between 30 and 66 years of age and the cohort was comprised of white (62%), black (19%), Hispanic (12%), Asian (4%) and other (3%) individuals. At the time of the study individuals in the LVL group were on highly active antiretroviral therapies (HAART), while subjects with HVL fell into one of three categories: on HAART (15); scheduled treatment interruption (6) or HAART naïve (1) (Table 1).

INSTRUMENT(S): GE Healthcare/Amersham Biosciences CodeLink Human Whole Genome Bioarray

SUBMITTER: Bing Sun   

PROVIDER: GSE18464 | GEO | 2009-10-09

SECONDARY ACCESSION(S): PRJNA118189

REPOSITORIES: GEO

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Publications

Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection.

Rempel Hans H   Sun Bing B   Calosing Cyrus C   Pillai Satish K SK   Pulliam Lynn L  

AIDS (London, England) 20100601 10


HIV-1 infection dysregulates the innate immune system and alters leukocyte-gene expression. The objectives were two fold: to characterize the impact of HIV-1 infection on peripheral monocyte gene expression and to identify the predominant factor(s) responsible for altered gene expression.In a cross-sectional study (n = 55), CD14 monocytes were isolated from 11 HIV-1 seronegative controls, 22 HIV-1 seropositive individuals with low-viral loads (LVL) and 22 HIV-1 seropositive individuals with high  ...[more]

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