MiR-142-5p/FAM134B Axis Manipulates ER-Phagy to Control PRRSV Replication

Kaifeng Guan1, Qiuju Su1, Kailin Kuang1

  • 1Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture, Huazhong Agricultural University, Wuhan, China.

Insights

Porcine reproductive and respiratory syndrome virus (PRRSV) subverts cell defense by downregulating ER-phagy receptor FAM134B. This mechanism promotes viral replication and offers new antiviral targets.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in the endoplasmic reticulum (ER).
  • Cellular ER homeostasis is maintained by ER-phagy (reticulophagy), which degrades stressed ER.
  • PRRSV infection disrupts ER homeostasis, necessitating investigation into its interaction with ER-phagy.

Purpose of the Study:

  • To investigate the role of ER-phagy in PRRSV replication.
  • To elucidate the mechanism by which PRRSV interacts with ER-phagy.
  • To identify potential antiviral targets related to ER-phagy.

Main Methods:

  • Investigated PRRSV's effect on ER-phagy receptor FAM134B.
  • Analyzed the role of PRRSV-induced miR-142-5p targeting FAM134B.
  • Utilized siRNA and mutant FAM134B protein to assess ER-phagy disruption.
  • Examined the impact of FAM134B-mediated ER-phagy on type I interferon signaling.

Main Results:

  • PRRSV infection downregulates ER-phagy receptor FAM134B.
  • PRRSV-induced miR-142-5p targets FAM134B, promoting viral replication.
  • Depletion or mutation of FAM134B disrupts ER-phagy and enhances PRRSV replication.
  • FAM134B-mediated ER-phagy activates type I interferon signaling, inhibiting PRRSV.

Conclusions:

  • ER-phagy plays a critical role in controlling PRRSV replication via FAM134B.
  • PRRSV subverts ER-phagy through FAM134B downregulation, facilitating viral pathogenesis.
  • Targeting the FAM134B-ER-phagy axis presents a potential strategy for PRRSV antiviral therapy.

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