Temporal activation of NF-κB regulates an interferon-independent innate antiviral response against cytoplasmic RNA viruses

被引:59
作者
Bose, S
Kar, N
Maitra, R
DiDonato, JA
Banerjee, AK
机构
[1] Cleveland Clin Fdn, Lerner Res Inst, Dept Virol, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA
关键词
D O I
10.1073/pnas.1832775100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
NF-kappaB is known to exert its antiviral innate immune response via the IFN-beta-induced Janus kinase/signal transducers and activators of transcription pathway. However, our current studies have demonstrated that activated NF-kappaB is capable of directly establishing an antiviral state independent of IFN or secreted soluble factor(s) against two highly pathogenic respiratory RNA viruses. Human parainfluenza virus type 3, a mildly cytopathic virus that induced NF-kappaB very early during infection was converted to a virulent virus after NF-kappaB inhibition. In contrast, a highly cytopathic virus, human respiratory syncytial virus that induced NF-kappaB late during infection, was converted to a mildly cytopathic virus after NF-kappaB induction before virus replication. This interconversion of cytopathic phenotypes of viruses after NF-kappaB modulation was further shown to be independent of IFN and soluble secreted factors(s). Moreover, tumor necrosis factor alpha (TNF-alpha) and IL-1beta elicited an antiviral response, which was NF-kappaB-dependent. Thus, NF-kappaB induction directly confers an essential innate antiviral response against human parainfluenza virus type 3 and respiratory syncytial virus, which is independent of IFN-inducible factor(s).
引用
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页码:10890 / 10895
页数:6
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