Classical Swine Fever Virus Envelope Glycoproteins E, E1, and E2 Activate IL-10-STAT1-MX1/OAS1 Antiviral Pathway Via Replacing Classical IFNα/β

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2025 Feb 26

PMID 40001503

Authors

Liyuan Zhang

Dongli Liang

Yu Tian

Jiaxin Liang

Xiaoquan Li

Cheng Liu

Jingjing Liang

Ting Rong Luo

Xiaoning Li

Affiliations

Soon will be listed here.

Abstract

Classical swine fever (CSF) is an acute and often fatal disease caused by CSF virus (CSFV) infection. In the present study, we investigated the transcriptional profiles of peripheral blood mononuclear cells (PBMCs) in pigs infected with CSFV. The results revealed that CSFV inhibits IFNα/β production, but up-regulates the expression of signal transducer and activator of transcription 1 (STAT1); this result was verified in vitro. Interestingly, STAT1 is typically a downstream target of IFNα/β, raising the question of how CSFV can inhibit IFNα/β expression, yet up-regulate STAT1 expression. To explore this further, we observed that UV-treated CSFV induced STAT1 expression. Our results demonstrated that CSFV E, E1, and E2 could up-regulate STAT1 expression within the host cell cytoplasm and facilitate its translocation into the nucleus. The E, E1, and E2 proteins also separately induced the up-regulation of interleukin (IL)-10; IL-10 acts as the communicator connecting E, E1, and E2 proteins to STAT1, leading to the subsequent up-regulation, phosphorylation, and nuclear translocation of STAT1. Silencing of IL-10 down-regulated STAT1 expression. Finally, MX1 and OAS1 were identified as downstream targets of the IL-10-STAT1 pathway. In summary, a novel IL-10-STAT1 pathway independent of IFNα/β induced by CSFV E, E1, and E2 was identified in this study.

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