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Published on: November 1, 2011
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.
Abstract:
Porcine reproductive and respiratory syndrome virus (PRRSV) can replicate its RNA genome in endoplasmic reticulum (ER) and utilize ER to facilitate its assembly and maturation. To maintain ER homeostasis, host cells initiate reticulophagy (known as ER-phagy) to effectively digest the stressed ER. In this study, we found that PRRSV infection subverted ER-phagy by downregulating ER-phagy receptor FAM134B. PRRSV-induced miR-142-5p directly targeted FAM134B and significantly promoted PRRSV replication. Meanwhile, siRNA-mediated depletion of FAM134B protein and overexpression of FAM134B mutant protein significantly disrupted ER-phagy and facilitated PRRSV replication. Furthermore, our results showed that FAM134B-mediated ER-phagy activated type I interferon signaling to inhibit PRRSV replication. Overall, this study reveals the important role of ER-phagy in PRRSV replication in a FAM134B-dependent manner. Our findings provide an insight into the pathogenesis of PRRSV and offer a theoretical basis for further development of antiviral therapeutic targets.
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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