| First Author | Zhang X | Year | 2016 |
| Journal | Cell Mol Immunol | Volume | 13 |
| Issue | 5 | Pages | 578-83 |
| PubMed ID | 27593482 | Mgi Jnum | J:325424 |
| Mgi Id | MGI:6852768 | Doi | 10.1038/cmi.2015.35 |
| Citation | Zhang X, et al. (2016) Neddylation is required for herpes simplex virus type I (HSV-1)-induced early phase interferon-beta production. Cell Mol Immunol 13(5):578-83 |
| abstractText | Type I interferons such as interferon-beta (IFN-beta) play essential roles in the host innate immune response to herpes simplex virus type I (HSV-1) infection. The transcription of type I interferon genes is controlled by nuclear factor-kappaB (NF-kappaB) and interferon regulatory factor (IRF) family members including IRF3. NF-kappaB activation depends on the phosphorylation of inhibitor of kappaB (IkappaB), which triggers its ubiqitination and degradation. It has been reported that neddylation inhibition by a pharmacological agent MLN4924 potently suppresses lipopolysaccharide (LPS)-induced proinflammatory cytokine production with the accumulation of phosphorylated IkappaBalpha. However, the role of neddylation in type I interferon expression remains unknown. Here, we report that neddylation inhibition with MLN4924 or upon UBA3 deficiency led to accumulation of phosphorylated IkappaBalpha, impaired IkappaBalpha degradation, and impaired NF-kappaB nuclear translocation in the early phase of HSV-1 infection even though phosphorylation and nuclear translocation of IRF3 were not affected. The blockade of NF-kappaB nuclear translocation by neddylation inhibition becomes less efficient at the later time points of HSV-1 infection. Consequently, HSV-1-induced early phase IFN-beta production significantly decreased upon MLN4924 treatment and UBA3 deficiency. NF-kappaB inhibitor JSH-23 mimicked the effects of neddylation inhibition in the early phase of HSV-1 infection. Moreover, the effects of neddylation inhibition on HSV-1-induced early phase IFN-beta production diminished in the presence of NF-kappaB inhibitor JSH-23. Thus, neddylation contributes to HSV-1-induced early phase IFN-beta production through, at least partially, promoting NF-kappaB activation. |
