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bioRxiv · 10.1101/392555

Bclaf1 critically regulates the type I interferon response and is degraded by alphaherpesvirus US3

Qin, C.·Zhang, R.·Lang, Y.·Shao, A.-w.·Xu, A.·Feng, W.·Han, J.·Wang, M.·He, W.·Yu, C.·Tang, J.
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Abstract

Type I interferon response plays a prominent role against viral infection, which is frequently disrupted by viruses. Here, we report Bcl-2 associated transcription factor 1 (Bclaf1) is degraded during the alphaherpesvirus Pseudorabies virus (PRV) and Herpes simplex virus type 1 (HSV-1) infections through the viral protein US3. We further reveal that Bclaf1 functions critically in type I interferon signaling. Knockdown or knockout of Bclaf1 in cells significantly impairs interferon- (IFN)-mediated gene transcription and viral inhibition against US3 deficient PRV and HSV-1. Mechanistically, Bclaf1 maintains a mechanism allowing STAT1 and STAT2 to be efficiently phosphorylated in response to IFN, and more importantly, facilitates IFN-stimulated gene factor 3 (ISGF3) binding with IFN-stimulated response elements (ISRE) for efficient gene transcription by directly interacting with ISRE and STAT2. Our studies establish the importance of Bclaf1 in IFN-induced antiviral immunity and in the control of viral infections.

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Qin, C., Zhang, R., Lang, Y., Shao, A.-w., Xu, A., Feng, W., Han, J., Wang, M., He, W., Yu, C., Tang, J.. 2018-08-16. Bclaf1 critically regulates the type I interferon response and is degraded by alphaherpesvirus US3. https://doi.org/10.1101/392555

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