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

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.

Glycyrrhiza polysaccharides inhibits PRRSV replication

“…Zhenbang [ 15 ] detected the content of N protein expressed by the ORF7 gene and analyzed that PRRSV infection could be inhibited by UPR induction. Kaifeng [ 16 ] detected the expression of PRRSV N protein in PAM by Western Blot and found that overexpression of FAM134B in PRRSV-infected cells could inhibit PRRSV replication. If GCP is used to inhibit the expression of the N protein, it will prevent the assembly of PRRSV, thereby inhibiting PRRSV replication.…”

Regulatory Non-Coding RNAs during Porcine Viral Infections: Potential Targets for Antiviral Therapy

“…Numerous studies have indicated that FAM134B is a significant limiting factor for viral replication and infection, such as by Ebola (EBOV), Dengue (DENV), West Nile (WNV), and Zika (ZIKA) [ 125 , 126 ]. Recent studies have shown that expression of FAM134B inhibits PRRSV infection by activating type I interferon signaling [ 127 ]. However, PRRSV infection is facilitated by up-regulation of miR-142-5p, which directly targets FAM134B expression to inhibit ER autophagy [ 127 ].…”

“…Recent studies have shown that expression of FAM134B inhibits PRRSV infection by activating type I interferon signaling [ 127 ]. However, PRRSV infection is facilitated by up-regulation of miR-142-5p, which directly targets FAM134B expression to inhibit ER autophagy [ 127 ]. This reveals another mechanism by which PRRSV achieves immune evasion by regulating miRNA expression, and also provides ideas for the treatment of PRRSV infection.…”

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

“…Autophagy is a critical process for maintaining cellular homeostasis and is often accompanied by endoplasmic reticulum (ER) stress. PRRSV can modify cellular membranes to serve as replication compartments, facilitating its assembly and maturation ( Guan et al., 2022 ). Autophagy is an antiviral host defense mechanism that targets viral particles and components to lysosomes for degradation, initiates innate immune responses, and promotes antigen presentation ( Li et al., 2020 ; Liang et al., 2021 ).…”