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Rubio D , Xu RH , Remakus S , Krouse TE , Truckenmiller ME , Thapa RJ , Balachandran S , Alcami A , Norbury CC , Sigal LJ
Crosstalk between the Type 1 Interferon and Nuclear Factor Kappa B Pathways Confers Resistance to a Lethal Virus Infection
Cell Host Microbe. 2013 Jun 12;13(6) :701-10
PMID: 23768494   
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Abstract
Nuclear factor kappa B (NF-kappaB) and type 1 interferon (T1-IFN) signaling are innate immune mechanisms activated upon viral infection. However, the role of NF-kappaB and its interplay with T1-IFN in antiviral immunity is poorly understood. We show that NF-kappaB is essential for resistance to ectromelia virus (ECTV), a mouse orthopoxvirus related to the virus causing human smallpox. Additionally, an ECTV mutant lacking an NF-kappaB inhibitor activates NF-kappaB more effectively in vivo, resulting in increased proinflammatory molecule transcription in uninfected cells and organs and decreased viral replication. Unexpectedly, NF-kappaB activation compensates for genetic defects in the T1-IFN pathway, such as a deficiency in the IRF7 transcription factor, resulting in virus control. Thus, overlap between the T1-IFN and NF-kappaB pathways allows the host to overcome genetic or pathogen-induced deficiencies in T1-IFN and survive an otherwise lethal poxvirus infection. These findings may also explain why some pathogens target both pathways to cause disease.
Notes
Rubio, Daniel Xu, Ren-Huan Remakus, Sanda Krouse, Tracy E Truckenmiller, Mary Ellen Thapa, Roshan J Balachandran, Siddharth Alcami, Antonio Norbury, Christopher C Sigal, Luis J P30 CA006927/CA/NCI NIH HHS/United States R01 AI065544/AI/NIAID NIH HHS/United States U19 AI083008/AI/NIAID NIH HHS/United States United States Cell host & microbe Nihms476150 Cell Host Microbe. 2013 Jun 12;13(6):701-10. doi: 10.1016/j.chom.2013.04.015.