Skip Navigation LinksHome > June 19, 2010 - Volume 24 - Issue 10 > Interferon-α drives monocyte gene expression in chronic unsu...
doi: 10.1097/QAD.0b013e32833ac623
Basic Science

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

Rempel, Hansa; Sun, Binga; Calosing, Cyrusa; Pillai, Satish Kb,c; Pulliam, Lynna,b,c,d

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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)-α, IFN-γ 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-α, IFN-γ or LPS demonstrated that IFN-α 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-α, whereas individuals with LVL have a nonactivated phenotype. In monocytes, there was no discernible expression profile linked to LPS exposure.

© 2010 Lippincott Williams & Wilkins, Inc.


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