Involvement of the IRF-1 transcription factor in antiviral responses to interferons.
The mechanisms underlying interferon (IFN)-induced antiviral states are not well understood. Interferon regulatory factor-1 (IRF-1) is an IFN-inducible transcriptional activator, whereas IRF-2 suppresses IRF-1 action. The inhibition of encephalomyocarditis virus (EMCV) replication by IFN-alpha and especially by IFN-gamma was impaired in cells from mice with a null mutation in the IRF-1 gene (IRF-1-/- mice). The IRF-1-/- mice were less resistant than normal mice to EMCV infection, as revealed by accelerated mortality and a larger virus titer in target organs. The absence of IRF-1 did not clearly affect replication of two other types of viruses. Thus, IRF-1 is necessary for the antiviral action of IFNs against some viruses, but IFNs activate multiple activation pathways through diverse target genes to induce the antiviral state.
Kimura
T
T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Nakayama
K
K
Penninger
J
J
Kitagawa
M
M
Harada
H
H
Matsuyama
T
T
Tanaka
N
N
Kamijo
R
R
Vilcek
J
J
Mak
T W
TW
D000818:Animals; D018188:Cardiovirus Infections / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004686:Encephalomyocarditis virus / Q000502:physiology; D005786:Gene Expression Regulation; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D018139:Simplexvirus / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014779:Virus Replication
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D016898:Interferon-alpha; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors; D007371:Interferon-gamma