The intricate interplay between RNA viruses and NF-κB

Schmitz, M. Lienhard; Kracht, Michael; Saul, Vera V.

doi:10.1016/j.bbamcr.2014.08.004

Cited by 63 publications

(63 citation statements)

References 165 publications

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“…The IKKβ inhibitor also partially suppressed viral replication by about 30% as assessed by measuring N protein levels ( Fig 5E). This result is in line with a positive role of IKKs for viral replication that may proceed through substrates unrelated to NF-κB as shown for a few other RNA viruses [20]. However, the inhibitory effects of PHA-408 at the mRNA and chromatin levels were stronger than the suppression of viral protein synthesis, suggesting that the IKK-NF-κB pathway may also exert pro-viral functions (Fig 5E-5G).…”

Section: Modulation Of Nf-κb Signaling By Hcov-229e and Functional Resupporting

confidence: 85%

The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells

et al. 2017

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Coronavirus replication takes place in the host cell cytoplasm and triggers inflammatory gene expression by poorly characterized mechanisms. To obtain more insight into the signals and molecular events that coordinate global host responses in the nucleus of coronavirus-infected cells, first, transcriptome dynamics was studied in human coronavirus 229E (HCoV-229E)-infected A549 and HuH7 cells, respectively, revealing a core signature of upregulated genes in these cells. Compared to treatment with the prototypical inflammatory cytokine interleukin(IL)-1, HCoV-229E replication was found to attenuate the inducible activity of the transcription factor (TF) NF-κB and to restrict the nuclear concentration of NF-κB subunits by (i) an unusual mechanism involving partial degradation of IKKβ, NEMO and IκBα and (ii) upregulation of TNFAIP3 (A20), although constitutive IKK activity and basal TNFAIP3 expression levels were shown to be required for efficient virus replication. Second, we characterized actively transcribed genomic regions and enhancers in HCoV-229E-infected cells and systematically correlated the genome-wide gene expression changes with the recruitment of Ser5-phosphorylated RNA polymerase II and prototypical histone modifications (H3K9ac, H3K36ac, H4K5ac, H3K27ac, H3K4me1). The data revealed that, in HCoV-infected (but not IL-1-treated) cells, an extensive set of genes was activated without inducible p65 NF-κB being recruited. Furthermore, both HCoV-229E replication and IL-1 were shown to upregulate a small set of genes encoding immunomodulatory factors that bind p65 at promoters and require IKKβ activity and p65 for expression. Also, HCoV-229E and IL-1 activated a common set of 440 p65-bound enhancers that differed from another 992 HCoV-229E-specific enhancer regions by distinct TF-binding motif combinations. Taken together, the study shows that cytoplasmic RNA viruses fine-tune NF-κB signaling at multiple levels and profoundly reprogram the host cellular chromatin landscape, thereby orchestrating the timely coordinated expression of genes involved in multiple signaling, immunoregulatory and metabolic processes.

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Section: Modulation Of Nf-κb Signaling By Hcov-229e and Functional Resupporting

confidence: 85%

The NF-κB-dependent and -independent transcriptome and chromatin landscapes of human coronavirus 229E-infected cells

et al. 2017

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“…Several proteins encoded by NF-κB target genes are involved in the activation of immune and inflammatory responses. NF-κB activation during viral infection is interpreted as a host protective response to viral pathogens (Schmitz et al, 2014). Type I interferons (IFNs) also play an important role in the immune response to viruses.…”

Section: Introductionmentioning

confidence: 99%

Dual NDP52 Function in Persistent CSFV Infection

Fan

Luo

et al. 2020

Front. Microbiol.

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Viruses have evolved many mechanisms to escape host antiviral responses. Previously, we found that classical swine fever virus (CSFV) infection induces autophagy using the autophagosome as a self-replication site, thereby evading the host immune response and promoting long-term infection. However, the underlying mechanisms used by CSFV to enter autophagosomes and the mechanism by which autophagy promotes viral replication remain unclear. We found that CSFV infection inhibited autophagy receptor nuclear dot protein 52 kDa (NDP52) expression, ubiquitination, and SUMO2-4 modification. Further analyses revealed that CSFV mediated ubiquitination and SUMOylation of NDP52 via Pten-induced kinase 1 (PINK1)-Parkin. Moreover, NDP52 inhibition also inhibited CSFV replication and the induction of mitophagy marker proteins expression. Inhibition of NDP52 reduced CD63 expression and binding to CSFV E2 protein, which has an essential role in persistent CSFV infection. As NDP52 has a close relationship with the NF-κB innate immunity pathway and plays an important role in the antiviral response, we investigated whether NDP52 inhibited CSFV replication through the release of immune factors and antivirus signals. Our results showed that inhibiting NDP52 boosted interferon and TNF release and promoted NF-κB pathway activation. In summary, we found that NDP52 inhibition not only reduces CSFV binding and entry into autophagic vesicles, but also inhibits CSFV replication by active NF-κB antiviral immune pathways. Our data reveal a novel mechanism by which NDP52, an autophagy receptor, mediates CSFV infection, and provide new avenues for the development of antiviral strategies.

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“…On the other hand, the replication of a reassortant SC35 expressing the HA segment from SC35M was enhanced Ͼ10,000-fold upon deletion of the p65 protein, emphasizing that the role of this transcription factor in IAV spread depends on the viral genotype. This may also explain in part the conflicting results assigning either pro-or antiviral functions for NF-B, as discussed in detail in a recent review (42). It will thus be very relevant in future studies to carefully consider the contribution of virus genetics to the specific effect of the NF-B system on IAV replication in a given host (cells).…”

Section: Discussionmentioning

confidence: 99%