title: Hepatitis C virus induces interferon-λ and interferon-stimulated genes in primary liver cultures.
abstract: Hepatitis C virus (HCV) replication in primary liver cells is less robust than that in hepatoma cell lines, suggesting that innate antiviral mechanisms in primary cells may limit HCV replication or spread. Here we analyzed the expression of 47 genes associated with interferon (IFN) induction and signaling following HCV infection of primary human fetal liver cell (HFLC) cultures from 18 different donors. We report that cell culture-produced HCV (HCVcc) induced expression of Type III (λ) IFNs and of IFN-stimulated genes (ISGs). Little expression of Type I IFNs was detected. Levels of IFNλ and ISG induction varied among donors and, often, between adapted and nonadapted HCV chimeric constructs. Higher levels of viral replication were associated with greater induction of ISGs and of λ IFNs. Gene induction was dependent on HCV replication, as ultraviolet light-inactivated virus was not stimulatory and an antiviral drug, 2'-C-methyladenosine, reduced induction of λ IFNs and ISGs. The level of IFNλ protein induced was sufficient to inhibit HCVcc infection of naïve cultures.
  
  
  CONCLUSIONS
  Together, these results indicate that despite its reported abilities to blunt the induction of an IFN response, HCV infection is capable of inducing antiviral cytokines and pathways in primary liver cell cultures. Induction of ISGs and λ IFNs may limit the growth and spread of HCV in primary cell cultures and in the infected liver. HCV infection of HFLC may provide a useful model for the study of gene induction by HCV in vivo.
authors.affiliation: Center for the Study of Hepatitis C, Laboratory of Virology and Infectious Disease, Rockefeller University, New York, NY 10065, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Marukian
authors.forename: Linda
authors.initials: L
authors.lastname: Andrus
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Sheahan
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Jones
authors.forename: Edgar D
authors.initials: ED
authors.lastname: Charles
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Dustin
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D007372:Interferons / Q000096:biosynthesis* / Q000494:pharmacology; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D053612:Janus Kinases / Q000378:metabolism; D008099:Liver / Q000166:cytology; D061251:Primary Cell Culture; D011994:Recombinant Proteins / Q000494:pharmacology; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D014779:Virus Replication / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000241:Adenosine; D007372:Interferons; D007378:Interleukins; D053612:Janus Kinases; D011994:Recombinant Proteins; C569537:2'-C-methyladenosine; C000624353:interferon-lambda, human; D000095022:Interferon Lambda