title: Monocyte activation in HIV/HCV coinfection correlates with cognitive impairment.
abstract: Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) challenges the immune system with two viruses that elicit distinct immune responses. Chronic immune activation is a hallmark of HIV infection and an accurate indicator of disease progression. Suppressing HIV viremia by antiretroviral therapy (ART) effectively prolongs life and significantly improves immune function. HIV/HCV coinfected individuals have peripheral immune activation despite effective ART control of HIV viral load. Here we examined freshly isolated CD14 monocytes for gene expression using high-density cDNA microarrays and analyzed T cell subsets, CD4 and CD8, by flow cytometry to characterize immune activation in monoinfected HCV and HIV, and HIV-suppressed coinfected subjects. To determine the impact of coinfection on cognition, subjects were evaluated in 7 domains for neuropsychological performance, which were summarized as a global deficit score (GDS). Monocyte gene expression analysis in HIV-suppressed coinfected subjects identified 43 genes that were elevated greater than 2.5 fold. Correlative analysis of subjects' GDS and gene expression found eight genes with significance after adjusting for multiple comparisons. Correlative expression of six genes was confirmed by qPCR, five of which were categorized as type 1 IFN response genes. Global deficit scores were not related to plasma lipopolysaccharide levels. In the T cell compartment, coinfection significantly increased expression of activation markers CD38 and HLADR on both CD4 and CD8 T cells but did not correlate with GDS. These findings indicate that coinfection is associated with a type 1 IFN monocyte activation profile which was further found to correlate with cognitive impairment, even in subjects with controlled HIV infection. HIV-suppressed coinfected subjects with controlled HIV viral load experiencing immune activation could benefit significantly from successful anti-HCV therapy and may be considered as preferential candidates.
authors: Department of Laboratory Medicine, Veterans Affairs Medical Center, San Francisco, California, USA.
authors: Hans
authors: H
authors: Rempel
authors: Bing
authors: B
authors: Sun
authors: Cyrus
authors: C
authors: Calosing
authors: Linda
authors: L
authors: Abadjian
authors: Alexander
authors: A
authors: Monto
authors: Lynn
authors: L
authors: Pulliam
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003072:Cognition Disorders / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000821:virology; D060085:Coinfection / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D003710:Demography; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides