Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses

Hua Tan, Jena Derrick, Jin Hong, Corneliu Sanda, William M. Grosse, Howard Edenberg, Milton Taylor, Scott Seiwert, Lawrence M. Blatt

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A role for type II interferon (IFN-γ) in resolving viral infection is suggested by the correlation of hepatitis C virus (HCV) clearance with enhancement of IFN-γ-producing activated T cells in the resolution of acute HCV infection. Using vesicular stomatitis virus (VSV), a synergistic direct antiviral effect was documented using IFN-γ1b and a potent, consensus type IIFN (IFN alfacon-1). Global expression profiling following EC50 exposure to IFN alfacon-1, IFN-γ1b, or a cocktail of the two allowed the antiviral state to be correlated with induction of a subset of IFN-stimulated genes (ISGs). Genes identified through this analysis corresponded to classic antiviral components, ISGs more recently associated with direct antiviral functions, as well as expressed sequence tags (ESTs) and hypothetical proteins. The magnitude of these antiviral EC50-correlated expression events in human hepatoma (Huh7) cells exposed to clinically relevant doses of IFN alfacon-1, IFN-γ1b, or a cocktail of the two was also probed because the standard of care for patients with chronic hepatitis C is type I IFN-containing regimens. Relative to type I IFNs used alone, the addition of type II IFN caused enhanced expression not only of many of the genes correlated with the direct antiviral state but also of genes involved in (1) antigen presentation to cytotoxic T lymphocytes (CTLs), (2) macrophage, natural killer (NK), and T helper 1 (ThI) cell recruitment and activation, (3) complement system function, (4) apoptosis, and (5) ISGs with unknown functions. As many of these processes are correlated clinically with resolution of chronic HCV infection, the combined use of these IFNs could display a beneficial effect on viral clearance in patients infected with HCV and other viruses through enhancement of one of these processes or of the direct antiviral state.

Original languageEnglish
Pages (from-to)632-649
Number of pages18
JournalJournal of Interferon and Cytokine Research
Volume25
Issue number10
DOIs
StatePublished - Oct 2005

Fingerprint

Interferon Type I
Interferon-gamma
Antiviral Agents
Hepacivirus
Virus Diseases
Interferons
Genes
Chronic Hepatitis C
Viruses
Vesicular Stomatitis
Th1 Cells
Complement C3
Complement Activation
Expressed Sequence Tags
Antigen Presentation
Cytotoxic T-Lymphocytes
Standard of Care
Hepatocellular Carcinoma
Macrophages
Apoptosis

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses. / Tan, Hua; Derrick, Jena; Hong, Jin; Sanda, Corneliu; Grosse, William M.; Edenberg, Howard; Taylor, Milton; Seiwert, Scott; Blatt, Lawrence M.

In: Journal of Interferon and Cytokine Research, Vol. 25, No. 10, 10.2005, p. 632-649.

Research output: Contribution to journalArticle

Tan, Hua ; Derrick, Jena ; Hong, Jin ; Sanda, Corneliu ; Grosse, William M. ; Edenberg, Howard ; Taylor, Milton ; Seiwert, Scott ; Blatt, Lawrence M. / Global transcriptional profiling demonstrates the combination of type I and type II interferon enhances antiviral and immune responses at clinically relevant doses. In: Journal of Interferon and Cytokine Research. 2005 ; Vol. 25, No. 10. pp. 632-649.
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