title: Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes.
abstract: Interleukin-28A (IL-28A), IL-28B and IL-29 are a family of class II cytokines that stimulate antiviral responses through a heterodimeric receptor that is distinct from the type I interferon (IFN) receptor. To better understand how this newly described family of cytokines regulates the antiviral state, we compared various cellular responses elicited by IL-29 and IFN-alpha. Here we show that these cytokines stimulate similar patterns of signal transducer and activator of transcription 1 (STAT-1), -2, -3, and -5 phosphorylation and nearly identical patterns of gene expression when analyzed in two distinct cell types by microarray analysis. Interestingly, the IL-29 receptor is preferentially expressed on primary hepatocytes within normal liver and pegylated forms of IL-29 and IFN-alpha induced equivalent 2'5' oligoadenylate synthetase (OAS) and MX1 gene expression in this cell type. Pegylated IL-29 also produced a significant reduction in human hepatitis B and hepatitis C viral load in vitro and reduced the cytopathic effect caused by the fully replicating flavivirus, West Nile virus. In conclusion, IL-29 and IFN-alpha stimulate identical antiviral responses despite their utilization of different receptors. This fact, combined with significant receptor expression in hepatitis virus-infected livers, suggests that IL-29 may have therapeutic value against chronic viral hepatitis in human patients.
authors.affiliation: ZymoGenetics, Inc., Seattle, WA 98102, USA.
authors.forename: Sean E
authors.initials: SE
authors.lastname: Doyle
authors.forename: Heidi
authors.initials: H
authors.lastname: Schreckhise
authors.forename: Kien
authors.initials: K
authors.lastname: Khuu-Duong
authors.forename: Katherine
authors.initials: K
authors.lastname: Henderson
authors.forename: Robert
authors.initials: R
authors.lastname: Rosler
authors.forename: Harold
authors.initials: H
authors.lastname: Storey
authors.forename: Lena
authors.initials: L
authors.lastname: Yao
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Fariba
authors.initials: F
authors.lastname: Barahmand-pour
authors.forename: Pallavur
authors.initials: P
authors.lastname: Sivakumar
authors.forename: Chung
authors.initials: C
authors.lastname: Chan
authors.forename: Carl
authors.initials: C
authors.lastname: Birks
authors.forename: Don
authors.initials: D
authors.lastname: Foster
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Clegg
authors.forename: Perdita
authors.initials: P
authors.lastname: Wietzke-Braun
authors.forename: Sabine
authors.initials: S
authors.lastname: Mihm
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Klucher
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016466:CHO Cells / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000494:pharmacology* / Q000627:therapeutic use; D005416:Flavivirus / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016174:Hepacivirus / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D006525:Hepatitis, Viral, Human / Q000188:drug therapy* / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000494:pharmacology* / Q000627:therapeutic use; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D012313:RNA / Q000032:analysis / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012313:RNA; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C000624353:interferon-lambda, human; D000095022:Interferon Lambda