2. Academic Validation
  3. Retinol binding protein 4 restricts PCV2 replication via selective autophagy degradation of viral ORF1 protein

Retinol binding protein 4 restricts PCV2 replication via selective autophagy degradation of viral ORF1 protein

  • Commun Biol. 2024 Nov 5;7(1):1438. doi: 10.1038/s42003-024-07052-1.
Qingbing Han 1 2,  Hejiao Zhao 1 2,  Meng Chen 1 2,  Wenshuo Xue 1 2,  Jun Li 3,  Lei Sun 4,  Yingli Shang 5 6 7
Affiliations

Affiliations

  • 1 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, China.
  • 2 Shandong Provincial Key Laboratory of Zoonoses, Shandong Agricultural University, Taian, Shandong, China.
  • 3 Division of Swine Diseases, Shandong Provincial Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China.
  • 4 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • 5 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Taian, Shandong, China. shangyl@sdau.edu.cn.
  • 6 Shandong Provincial Key Laboratory of Zoonoses, Shandong Agricultural University, Taian, Shandong, China. shangyl@sdau.edu.cn.
  • 7 Institute of Immunology, Shandong Agricultural University, Taian, Shandong, China. shangyl@sdau.edu.cn.
PMID: 39500783 DOI: 10.1038/s42003-024-07052-1
Abstract

Autophagy is a highly conserved degradative process that has been linked to various functions, including defending host cells against pathogens. Although the involvement of Autophagy in porcine circovirus 2 (PCV2) Infection has become apparent, it remains unclear whether selective Autophagy plays a critical role in PCV2 restriction. Here we show that retinol-binding protein 4 (RBP4), an adipokine for retinol carrier, initiates the autophagic degradation of PCV2 ORF1 protein. PCV2 Infection increases RBP4 protein levels through MAPK-eIF4E axis in living cells. Ectopic expression of RBP4 or recombinant RBP4 treatment promotes the degradation of ORF1 protein. Mechanistically, RBP4 activates TRAF6 to induce K63-linked ubiquitination of ORF1, leading to SQSTM1/p62-mediated selective Autophagy for degradation. Consequently, RBP4 deficiency increases viral loads and exacerbates the pathogenicity of PCV2 in vivo. Collectively, these results identify RBP4 as a key host restriction factor of PCV2 and reveal a previously undescribed Antiviral mechanism against PCV2 in infected cells.

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