title: Interferon-alpha drives monocyte gene expression in chronic unsuppressed HIV-1 infection.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Laboratory Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Rempel
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Cyrus
authors.initials: C
authors.lastname: Calosing
authors.forename: Satish K
authors.initials: SK
authors.lastname: Pillai
authors.forename: Lynn
authors.initials: L
authors.lastname: Pulliam
mesh_terms: D003430:Cross-Sectional Studies; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D016898:Interferon-alpha / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha; D014481:United States; D019562:Viral Load
chemical_list: D016898:Interferon-alpha; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha