Interleukin-27, an anti-HIV-1 cytokine, inhibits replication of hepatitis C virus.
Interleukin (IL)-27 is a member of IL-12 family cytokine. We have previously reported that IL-27 inhibits human immunodeficiency virus type-1 (HIV-1) replication in CD4(+) T cells and monocyte-derived macrophages, even though IL-12 enhances HIV-1 replication in primary CD4(+) T cells. Further study demonstrates that IL-27 induces antiviral genes including RNA-dependent protein kinase, oligoadenylate synthetase, and myxovirus protein in the same manner as interferon (IFN)-alpha. Neutralization assay using anti-IFN antibodies, real-time RT-PCR, and enzyme-linked immunosorbent assay demonstrated that IL-27 induces the antiviral genes without the induction of IFNs. IFN-alpha has been administered to hepatitis C virus (HCV)-infected patients as well as HCV/HIV-1 co-infected patients. Despite the improved immunotherapy, some patients are still failed to respond to the treatment. Since IL-27 induces IFN-alpha-like responses including the induction of antiviral genes, it was speculated that IL-27 may impact the replication of HCV. In this study, we evaluated the role of IL-27 on HCV replication using Huh7.5, an HCV permissive cell line. IL-27 induces STAT-1 and -3 in the cell line, and dose-dependently inhibited HCV. These data suggest that IL-27 may play a role in the development of a novel immunotherapeutic strategy for HCV and HCV/HIV co-infection.
Frank
Astrid C
AC
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Zhang
Xiaozhen
X
Katsounas
Antonios
A
Bharucha
Jennifer P
JP
Kottilil
Shyamasundaran
S
Imamichi
Tomozumi
T
D000998:Antiviral Agents / Q000627:therapeutic use; D002460:Cell Line; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015497:HIV-1 / Q000276:immunology; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D022781:Hepatocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology*; D050791:STAT Transcription Factors / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
D000998:Antiviral Agents; D020381:Interleukin-17; D050791:STAT Transcription Factors