title: Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV.
abstract: BACKGROUND
  Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance.
  
  
  METHODS
  Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV.
  
  
  RESULTS
  We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05) before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are associated with innate immune response functions.
  
  
  CONCLUSIONS
  These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA. cheny@pitt.edu.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA.
authors.forename: Chengli
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA.
authors.forename: Debjani
authors.initials: D
authors.lastname: Guha
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.affiliation: Department of Pathology, VA Hospital, Pittsburgh, Pa, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Kulich
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA.
authors.forename: Aiymkul
authors.initials: A
authors.lastname: Ashimkhanova
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Rinaldo
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Seaberg
authors.affiliation: Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
authors.affiliation: Division of Infectious Diseases, School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Stosor
authors.affiliation: Department of Epidemiology, UCLA Fielding School of Public Health, and Departments of Obstetrics & Gynecology and Microbiology, Immunology & Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, 2138 Parran Hall, 130 DeSoto Street, Pittsburgh, Pa, 15261, USA.
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
mesh_terms: D060085:Coinfection / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000821:virology*; D006526:Hepatitis C / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load
chemical_list: D012367:RNA, Viral
keywords: Chronic HCV infection; Clearance of HCV infection; HIV/HCV coinfection; Plasma RNA sequencing; Sequence analysis