title: Chronic immune activation is a distinguishing feature of liver and PBMC gene signatures from HCV/HIV coinfected patients and may contribute to hepatic fibrogenesis.
abstract: Hepatitis C virus/human immunodeficiency virus (HCV/HIV) coinfected patients demonstrate accelerated progression to severe liver injury in comparison to HCV monoinfected patients, although the underlying mechanisms are unclear owing to infection of separate tissue compartments with two distinct viral pathogens. Microarray analysis of paired liver biopsy and peripheral blood mononuclear cell (PBMC) specimens from HCV/HIV coinfected and HCV monoinfected patients identified a gene expression signature associated with increased inflammation and immune activation that was present only in liver and PBMC samples from coinfected patients. We also identified in these samples liver- and PBMC-specific signatures enriched with fibrogenic/hepatic stellate activation and proinflammatory genes, respectively. Finally, Bayesian networks were constructed by assimilating these data with existing data from liver and PBMC samples from other cohorts, augmenting enrichment of biologically important pathways and further indicating that chronic immune activation in HCV/HIV coinfection may exacerbate liver disease progression in coinfected patients.
authors.affiliation: Department of Microbiology, University of Washington, Box 358070, Seattle, WA 98195, USA.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Rasmussen
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Wang
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Shuhart
authors.forename: Sean C
authors.initials: SC
authors.lastname: Proll
authors.forename: Yudong
authors.initials: Y
authors.lastname: He
authors.forename: Razvan
authors.initials: R
authors.lastname: Cristescu
authors.forename: Chris
authors.initials: C
authors.lastname: Roberts
authors.forename: Victoria S
authors.initials: VS
authors.lastname: Carter
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Williams
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Diamond
authors.forename: Janine T
authors.initials: JT
authors.lastname: Bryan
authors.forename: Roger
authors.initials: R
authors.lastname: Ulrich
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Korth
authors.forename: Lisa V
authors.initials: LV
authors.lastname: Thomassen
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D000328:Adult; D001706:Biopsy; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D055166:Hepatic Stellate Cells / Q000276:immunology; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged
chemical_list: D016207:Cytokines