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Conflict of interest The authors state no conflict of interest.

The biology of type I IFNs

Early changes in natural killer cell function indicate virologic response to interferon therapy for hepatitis C. Distinct signature type I interferon responses are determined by the infecting virus and the target cell. Accessing the therapeutic potential of immunostimulatory nucleic acids. Improved vaccine protection against retrovirus infection after co-administration of adenoviral vectors encoding viral antigens and type I interferon subtypes.

Interferon induces natural killer cell blastogenesis in vivo. The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon. J Interferon Cytokine Res. Interferon alfa subtypes and levels of type I interferons in the liver and peripheral mononuclear cells in patients with chronic hepatitis C and controls. Type I interferon gene therapy protects against cytomegalovirus-induced myocarditis. Type I interferon differential therapy for erythroleukemia: Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.

The early interferon alpha subtype response in infant macaques infected orally with SIV. J Acquir Immune Defic Syndr. Cytokines increase transporter in antigen processing-1 expression more rapidly than HLA class I expression in endothelial cells. Interferon-beta is required for interferon-alpha production in mouse fibroblasts.

Mechanism of action of interferon and ribavirin in treatment of hepatitis C. IFN-alpha subtypes differentially affect human T cell motility. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. Detection of differential expression of mouse interferon-alpha subtypes by polymerase chain reaction using specific primers. Impact of protein kinase PKR in cell biology: Microbiol Mol Biol Rev. Anti-retroviral effects of type I IFN subtypes in vivo.

Interferon alpha subtype 11 activates NK cells and enables control of retroviral infection. Polyinosinic-polycytidylic acid treatment of Friend retrovirus-infected mice improves functional properties of virus-specific T cells and prevents virus-induced disease. Induction of innate immunity against herpes simplex virus type 2 infection via local delivery of toll-like receptor ligands correlates with beta interferon production.

Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. Interferon-induced Mx proteins in anti-viral host defense. Characterization of the type I interferon locus and identification of novel genes. Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon. Differential responses to IFN-alpha subtypes in human T cells and dendritic cells.

Expression profiles of human interferon-alpha and interferon-lambda subtypes are ligand- and cell-dependent. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.

Randomized, controlled trial of recombinant human alpha-interferon in patients with chronic hepatitis B. Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. Treatment of acute hepatitis C with interferon alfa-2b. Differential receptor subunit affinities of type I interferons govern differential signal activation. Cytosolic DNA sensors regulating type I interferon induction. Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection.

Divergent activities of interferon-alpha subtypes against intracellular hepatitis C virus replication.

IFN-α subtypes: distinct biological activities in anti-viral therapy

CpG oligodeoxynucleotides allow for effective adoptive T-cell therapy in chronic retroviral infection. Binding and activity of all human alpha interferon subtypes. Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Novel growth and death related interferon-stimulated genes ISGs in melanoma: Alpha-interferon structure and natural killer cell stimulatory activity.

Biological assays for interferons.

IFN-alpha expression and anti-viral effects are subtype and cell type specific in the cardiac response to viral infection. Anti-hepatitis C virus activity of albinterferon alfa-2b in cell culture. Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIVspecific T cell responses.

Type I Interferon Signal Pathway

Molecular characterization of woodchuck type I interferons and their expression by woodchuck peripheral blood lymphocytes. Relative sensitivity of hepatitis B virus and other hepatotropic viruses to the anti-viral effects of cytokines. Combination therapy with interferon plus ribavirin for the initial treatment of chronic hepatitis C. Phase 1B, randomized, double-blind, dose-escalation trial of CPG in patients with chronic hepatitis C virus. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a.

Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor Microarray analyses of differentially expressed human genes and biological processes in ECV cells infected with rubella virus. The differential activity of interferon-alpha subtypes is consistent among distinct target genes and cell types. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Albinterferon Alfa-2b was not inferior to pegylated interferon-alpha in a randomized trial of patients with chronic hepatitis C virus genotype 2 or 3.

Hepatitis C viral dynamics in vivo and the anti-viral efficacy of interferon-alpha therapy. Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther.

Editorial Reviews

A comparison of interferon-Con1 with natural recombinant interferons-alpha: Characterization of interferon-alpha 13, a novel constitutive murine interferon-alpha subtype. Characterization of the murine alpha interferon gene family. Oral resiquimod in chronic HCV infection: Boceprevir for untreated chronic HCV genotype 1 infection.

NK cell trafficking and cytokine expression in splenic compartments after IFN induction and viral infection. Efficacy of a week course of PEG-interferon alpha-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance. In vitro sensitivity of human metapneumovirus to type I interferons.

Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Response-guided telaprevir combination treatment for hepatitis C virus infection. How cells respond to interferons.

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