Bluetongue virus non-structural protein 3 (NS3) and NS4 coordinatively antagonize type Ⅰ interferon signaling by targeting STAT1.

Publisher: Elsevier Scientific Pub. Co Country of Publication: Netherlands NLM ID: 7705469 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2542 (Electronic) Linking ISSN: 03781135 NLM ISO Abbreviation: Vet Microbiol Subsets: MEDLINE

Original Publication: Amsterdam, Elsevier Scientific Pub. Co.

Host-Pathogen Interactions*/genetics ; Host-Pathogen Interactions*/immunology ; Signal Transduction*; Bluetongue virus/*genetics ; Bluetongue virus/*metabolism ; Interferon Type I/*antagonists & inhibitors ; STAT1 Transcription Factor/*metabolism ; Viral Nonstructural Proteins/*metabolism; Cell Line ; HEK293 Cells ; HeLa Cells ; Humans ; Immune Evasion ; Immunity, Innate ; Interferon Type I/genetics ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Phosphorylation ; STAT1 Transcription Factor/genetics ; Viral Nonstructural Proteins/genetics ; Viral Nonstructural Proteins/immunology

Previous studies have pointed out that bluetongue virus (BTV) down-regulates the expression levels of type Ⅰ interferon (IFN-Ⅰ) and inhibits IFN-Ⅰ signaling by targeting on the Janus tyrosine kinase (JAK)-signal transducer and activator of transcription protein (STAT) pathway. However, individual viral protein could not effectively block IFN-Ⅰ signaling. There is a need to explore the underlying mechanisms by which viral proteins of BTV coordinate to antagonize the IFN-Ⅰ signaling. We investigated the coordinative role of BTV-1 nonstructural protein 3 (NS3) and NS4 in counteracting IFN-Ⅰ signaling in the JAK-STAT pathway by directly interacting with STAT1. The NS3 and NS4 targeted the SH2 domain of STAT1 to inhibit its phosphorylation, heterodimerization, nuclear translocation, as well as activation of downstream genes of the JAK-STAT pathway. NS3 and NS4 impaired STAT1 phosphorylation induced by IFN-Ⅰ in a dose dependent manner. Overall, this study confirmed that NS3 and NS4 of BTV participate in interfering with IFN-Ⅰ signaling process. Also, a new mechanism employed by BTV to evade host innate immune responses was revealed.
(Copyright © 2021 Elsevier B.V. All rights reserved.)

Keywords: Bluetongue virus; Interferon; Non-structural protein; Phosphorylation; STAT1

0 (Interferon Type I)
0 (S10 protein, Bluetongue virus)
0 (STAT1 Transcription Factor)
0 (STAT1 protein, human)
0 (Viral Nonstructural Proteins)

Date Created: 20210124 Date Completed: 20210902 Latest Revision: 20210902

20240829

10.1016/j.vetmic.2021.108986

33486325