2. Academic Validation
  3. Mitochondrial protein COX5B orchestrates antiviral autophagy and apoptosis to restrict SRBSDV propagation in Sogatella furcifera

Mitochondrial protein COX5B orchestrates antiviral autophagy and apoptosis to restrict SRBSDV propagation in Sogatella furcifera

  • Autophagy. 2025 Dec 24:1-19. doi: 10.1080/15548627.2025.2601863.
Qing Bai 1 2,  Yawen Ban 1 2,  Lifei Zhao 1 2,  Ting Cui 1 2,  Xue Li 1 2,  Tong Zhang 3 4,  Guohui Zhou 3 4,  Qingfa Wu 1 2
Affiliations

Affiliations

  • 1 Department of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  • 2 Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, University of Science and Technology of China, Hefei, Anhui, China.
  • 3 National Key Laboratory of Green Pesticide, South China Agricultural University, Guangzhou, Guangdong, China.
  • 4 Guangdong Province Key Laboratory of Microbial Signals and Disease Control, College of Plant Protection, South China Agricultural University, Guangzhou, Guangdong, China.
PMID: 41358576 DOI: 10.1080/15548627.2025.2601863
Abstract

Southern rice black-streaked dwarf virus (SRBSDV), a devastating plant pathogen transmitted by Sogatella furcifera, subverts host cellular machinery to establish persistent Infection. While viral manipulation of mitochondrial dynamics and macroautophagic/autophagic pathways has been documented, host counterstrategies against such viral sabotage remain poorly understood. Here, we unveil a novel regulatory axis involving the viral protein P5-2, mitochondrial cytochrome c oxidase subunit COX5B, and the autophagy-related protein Atg3 during SRBSDV Infection in S. furcifera. SRBSDV P5-2 localizes to host mitochondria, inducing mild structural damage and triggering mitochondrial stress. In response, COX5B is transcriptionally and translationally upregulated, exacerbating mitochondrial dysfunction to amplify autophagic flux. This enhanced Autophagy facilitates the encapsulation of viral particles and damaged organelles within autophagosomes for subsequent lysosomal degradation. Intriguingly, COX5B directly interacts with P5-2, redirecting it to mitochondria and counteracting its autophagy-suppressive effects by sustaining Atg3-mediated autophagosome maturation. This interaction establishes COX5B as a molecular switch, tipping the balance toward antiviral Autophagy rather than viral exploitation of Mitophagy. Upregulation of COX5B induces suppression of class I phosphoinositide 3-kinase (PI3K)-Akt signaling pathway, which mitigates its autophagy-inhibitory effects and promotes Apoptosis to eliminate severely infected cells. Conversely, COX5B knockdown activates PI3K-Akt-mediated survival signaling, establishing a cytoprotective microenvironment that supports viral replication. Our study reveals a tripartite P5-2-COX5B-Atg3 axis modulating mitochondrial stress, Autophagy, and Apoptosis to balance viral persistence and host survival. This identifies COX5B as a central mitochondrial sentinel in insect Antiviral immunity, demonstrating how host factors counteract viral sabotage via direct protein interactions, suggesting targets to disrupt viral transmission cycles.Abbreviations: Akt/Protein Kinase B: Akt kinase; Atg3 Autophagy related 3; CcO: ytochrome c oxidase; COX5B: cytochrome c oxidase subunit 5B; dsCOX5B: double-stranded RNAs targeting COX5B; dsGFP: double-stranded RNAs targeting green fluorescent protein; FITC: fluorescein isothiocyanate; Hsp60A/HSPD1: Heat shock protein 60A; mTor: mechanistic target of rapamycin kinase; PI3K: phosphoinositide 3-kinase; RNAi: RNA interference; RT-qPCR: quantitative reverse transcription PCR; SRBSDV: Southern rice black-streaked dwarf virus; TEM: transmission electron microscopy; TRITC: tetramethylrhodamine; WBPH: white-backed planthopper (Sogatella furcifera) dsCOX5B: double-stranded RNAs targeting COX5B; dsGFP: double-stranded RNAs targeting green fluorescent protein; FITC: fluorescein isothiocyanate; Hsp60A/HSPD1: Heat shock protein 60A; mTor: mechanistic target of rapamycin kinase; PI3K: phosphoinositide 3-kinase; RNAi: RNA interference; RT-qPCR: quantitative reverse transcription PCR; SRBSDV: Southern rice black-streaked dwarf virus; TEM: transmission electron microscopy; TRITC: tetramethylrhodamine; WBPH: white-backed planthopper (Sogatella furcifera).

Keywords

Antiviral autophagy; COX5B; PI3K-Akt-mTor pathway; SRBSDV; host-virus interaction; sogatella furcifera.

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