title: Differential Specificity of Interferon-alpha Inducible Gene Expression in Association with Human Immunodeficiency Virus and Hepatitis C Virus Levels and Declinesin vivo.
abstract: OBJECTIVE
  This study was aimed to correlatein vivointerferon (IFN) inducible gene (IFIG) expression and IFIG induction with viral-load (VL) and VL-kinetics of Human-Immunodeficiency-Virus (HIV) or Hepatitis-C-Virus (HCV) in HIV-positive patients treated with pegylated IFN-alpha-2a (PegIFNα).
  
  
  METHODS
  HIV mono-infected patients (N=8) and HIV/HCV co-infected patients (N=23, without HIV-viremia) were treated with PegIFNα (180 μg/week) for 12 and 48 weeks, respectively. Blood sampling for monitoring IFIG expression occurred at day_0 and week_3, _6 and _12 for HIV mono-infected patients vs. only at day_0 and week_48 for HIV/HCV co-infected subjects. IFIG expression (N=20) was measured in peripheral blood mononuclear cells by bDNA-assay. VL levels/changes in plasma were analyzed for correlation with IFIG expression/induction at/between selected time points. Overall, P<0.05 was considered significant.
  
  
  RESULTS
  None of the 20 IFIG expression profiles at day_0 correlated significantly with HIV-VL at day_0. Expression at day_0 of 3 IFIG (APOBEC3G/OAS1/OAS2) correlated significantly (r>+0.42/P<0.05) with HCV-VL at day_0. The strongest antiviral effect [measured as median viral decline per week: ΔVL/week (log10)] occurred in common against HIV and HCV between day_0 and week_3 during 12 weeks of continuous PegIFNα treatment in both cohorts. Expression at day_0 of 1 IFIG (APOBEC3A) correlated significantly (r<-0.71/P<0.05) with HIV-ΔVL/week (log10) from day_0 to week_3. No significance was reached in correlations between expression values of 20 IFIG at day_0 and HCV-ΔVL/week (log10) from day_0 to week_3. No significant correlation was detected between IFIG expression changes (ΔIFIG=induction) from day_0 to week_3 and HIV-ΔVL/week (log10) from day_0 to week_3. Interestingly, induction of 1 IFIG (ΔISG20) from day_0 to week_48 was significantly associated (P<0.05) with permanent HCV clearance.
  
  
  CONCLUSIONS
  This study demonstrates the differential specificity of PegIFNα mediated molecular actions by dissecting the kinetics of IFIG expression and induction, suggesting multiple, possibly non-overlapping mechanisms for antiviral effects against HCV and HIV.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany ; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA.
authors.forename: Antonios
authors.initials: A
authors.lastname: Katsounas
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA.
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Frank
authors.affiliation: Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Polis
authors.affiliation: Division of Infectious and Immunologic Diseases, UC Davis, Medical Center 4150 V Street, PSSB G500 Sacramento, CA 95817, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Asmuth
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Bethesda, MD 20892, USA.
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
keywords: Hepatitis C; Human Immunodeficiency Virus; Interferon inducible genes; Viral kinetics