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

ABSTRACT: OBJECTIVES: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. DESIGN AND METHODS: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-viral loads (HVL). Monocyte gene expression data were collected for control, LVL and HVL individuals using high-density microarrays. We evaluated three HIV-1 disease-related peripheral factors, interferon (IFN)-alpha, IFN-gamma and lipopolysaccharide (LPS) as candidates causing monocyte dysregulation, by comparing gene expression profiles between study individuals and monocytes treated with these factors in vitro. Plasma from HIV-1 positive individuals was quantified for LPS and soluble CD14. RESULTS:Monocytes from HIV-1-infected individuals with viral loads above 10,000 RNA copies/ml (HVL) displayed an activated phenotype. Characterization of gene expression revealed an ongoing immune response to viral infection including inflammation and chemotaxis. Gene expression analysis of in-vitro-treated HIV-1 seronegative monocytes with IFN-alpha, IFN-gamma or LPS demonstrated that IFN-alpha most accurately recapitulated the HIV-1 HVL profile. No LPS-induced gene expression signature was detected even in HIV-1 individuals with the highest LPS and sCD14 levels. CONCLUSION:Monocyte gene expression in individuals with HIV-1 viremia is predominantly due to IFN-alpha, whereas individuals with LVL have a nonactivated phenotype. In monocytes, there was no discernible expression profile linked to LPS exposure.

SUBMITTER: Rempel H

PROVIDER: S-EPMC2991092 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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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

<h4>Objectives</h4>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.<h4>Design and methods</h4>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) a ...[more]

PMID: 20495440

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

Publications

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

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