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Interferon- 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

doi: 10.1097/QAD.0b013e32833ac623
Basic Science

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.

aDepartments of Laboratory Medicine, USA

bMedicine, San Francisco Veterans Affairs Medical Center, USA

cDepartments of Medicine, USA

dLaboratory Medicine, University of California, San Francisco, California, USA.

Received 2 November, 2009

Revised 4 February, 2010

Accepted 8 April, 2010

Correspondence to Dr Lynn Pulliam, PhD, San Francisco Veterans Affairs Medical Center, USA. Tel: +1 415 221 4810 x6490; fax: +1 415 379 5647; e-mail: Lynn.Pulliam@ucsf.edu

© 2010 Lippincott Williams & Wilkins, Inc.