Porcine Reproductive and Respiratory Syndrome Virus Degrades TANK-binding Kinase 1 Via Chaperon-mediated Autophagy to Suppress Type I Interferon Production and Facilitate Viral Proliferation

Overview

Journal Vet Res

Publisher Biomed Central

Specialty Veterinary Medicine

Date 2024 Nov 15

PMID 39543624

Authors

Shuang-Shuang Zhao

Qisheng Qian

Yao Wang

Songlin Qiao

Rui Li

Affiliations

Soon will be listed here.

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) has led to significant economic losses in the global swine industry. Type I interferon (IFN-I) plays a crucial role in the host's resistance to PRRSV infection. Despite extensive research showing that PRRSV employs multiple strategies to antagonise IFN-I induction, the underlying mechanisms remain to be fully elucidated. In this study, we have discovered that PRRSV inhibits the production of IFN-I by degrading TANK-binding kinase 1 (TBK1) through chaperon-mediated autophagy (CMA). From a mechanistic standpoint, PRRSV nonstructural protein 2 (Nsp2) increases the interaction between the heat shock protein member 8 (HSPA8) and TBK1. This interaction leads to the translocation of TBK1 into lysosomes for degradation, mediated by lysosomal-associated membrane protein 2A (LAMP2A). As a result, the downstream activation of IFN regulatory factor 3 (IRF3) and the production of IFN-I are hindered. Together, these results reveal a new mechanism by which PRRSV suppresses host innate immunity and contribute to the development of new antiviral strategies against the virus.

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