Alpha interferon inhibits hepatitis C virus replication in primary human hepatocytes infected in vitro.
Chronic hepatitis C is a common cause of liver disease, the complications of which include cirrhosis and hepatocellular carcinoma. Treatment of chronic hepatitis C is based on the use of alpha interferon (IFN-alpha). Recently, indirect evidence based on mathematical modeling of hepatitis C virus (HCV) dynamics during human IFN-alpha therapy suggested that the major initial effect of IFN-alpha is to block HCV virion production or release. Here, we used primary cultures of healthy, uninfected human hepatocytes to show that: (i) healthy human hepatocytes can be infected in vitro and support HCV genome replication, (ii) hepatocyte treatment with IFN-alpha results in expression of IFN-alpha-induced genes, and (iii) IFN-alpha inhibits HCV replication in infected human hepatocytes. These results show that IFN-alpha acts primarily through its nonspecific antiviral effects and suggest that primary cultures of human hepatocytes may provide a good model to study intrinsic HCV resistance to IFN-alpha.
Castet
Valérie
V
INSERM U128, Montpellier, France.
Fournier
Chantal
C
Soulier
Alexandre
A
Brillet
Rozenn
R
Coste
Joliette
J
Larrey
Dominique
D
Dhumeaux
Daniel
D
Maurel
Patrick
P
Pawlotsky
Jean-Michel
JM
D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D016679:Genome, Viral; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008954:Models, Biological; D009154:Mutation; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins