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

Chao Qin,Wanwei He,Rui Zhang,Yue Lang,Jun Han,Anwen Shao,Cuilian Yu,Aotian Xu,Mengdong Wang,Wenhai Feng,Jun Tang,Pinghui Feng

doi:10.1371/journal.ppat.1007559

Chao Qin, Wanwei He + Show 10 more

Open Access

https://doi.org/10.1371/journal.ppat.1007559

Copy DOI

Journal: PLoS Pathogens	Publication Date: Jan 25, 2019
Citations: 40	License type: CC BY 4.0

Affiliation: China Agricultural University

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-α (IFNα) -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 IFNα, 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 IFNα-induced antiviral immunity and in the control of viral infections.

Highlights

Herpesviridae is a family of large DNA viruses with an ability to establish persistent infection in hosts
We further show that Bcl-2 associated transcription factor 1 (Bclaf1) is a novel regulator of IFN pathway by enhancing the IFN induced transcriptions of anti-viral genes
Since Bclaf1 is degraded in the proteasome upon HMCV infection, we examined if this was the case for Pseudorabies virus (PRV) and Herpes simplex virus type 1 (HSV-1)

Summary

Introduction

Herpesviridae is a family of large DNA viruses with an ability to establish persistent infection in hosts. Pseudorabies virus (PRV) and herpes simplex virus type 1 (HSV-1) belong to the alphaherpesvirus subfamily and the genera varicellovirus and simplexvirus, respectively. They are often used as model viruses to study alphaherpesvirus biology. HSV-1 is a human restricted virus, resulting in various mucocutaneous diseases, such as herpes labialis, genital herpes, herpetic whitlow, and keratitis [4]. It causes serious encephalitis in a small portion of the infected individuals [4]

Results

Discussion

Conclusion