PRRSV degrades MDA5 via dual autophagy receptors P62 and CCT2 to evade antiviral innate immunity

• DOI: 10.1016/j.virs.2024.01.005
• Publication Date: 2024-01-23T07:35:56Z
• Authors: Ruiqi Sun; Yanyu Guo; Lilin Zhang; Huixia Zhang; Boxuan Yin; Xiaoyang Li; Changyan Li; Liu Yang; Lei Zhang; Zexing Li; Jinhai Huang
• Keywords: MDA5; RIG-I

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economically devastating pathogen that has evolved various strategies to evade innate immunity. Downregulation of antiviral interferon largely contributes PRRSV immunoevasion through cytoplasmic melanoma differentiation-associated gene 5 (MDA5), receptor senses viral RNA. In this study, the downregulated transcription expression levels porcine MDA5 in infection were observed, but detailed mechanisms remain unclear. The interaction between P62 was strengthened due phosphorylation modification autophagic by upregulated kinase CK2α K63 ubiquitination catalyzed E3 ubiquitinase TRIM21 PRRSV-infected cells, thus triggering classic P62-mediated autophagy. Additionally, interacted with chaperonin containing TCP1 subunit 2 (CCT2) enhanced nsp3, facilitating aggregate formation clearance MDA5-CCT2-nsp3 independently ubiquitin. Enhanced degradation occurs via two pathways, including binding autophagy aggrephagy CCT2, intense immune suppression. research reveals novel mechanism evasion provides fundamental insights for development new vaccines or therapeutic strategies.