AFB1 exposure promotes SIV replication and lung damage via RIG-I- and p38-mediated RETREG1/FAM134B-dependent endoplasmic reticulum autophagy
Year: 2025
Type: article
Abstract: , qRT-PCR, and WB assays were used to detect SIV replication, after which proteomic detection was used to screen key proteins and pathways. Thirty piglets were subsequently randomly divided into 6 groups. The low-pathogenicity SIV was inoculated to establish a piglet model of SIV infection. Different doses of AFB1 were administered daily to SIV-infected piglets for 14 d. The in vitro results revealed that 0.02-0.04 μg/mL AFB1 markedly promoted SIV replication. Proteomic analysis revealed that reticulophagy regulator 1 (RETREG1/FAM134B) and p38 signaling were markedly upregulated, whereas RIG-I signaling was significantly downregulated. The above results were confirmed by qRT-PCR and WB assays. Transmission electron microscopy was used to further prove that AFB1 promoted endoplasmic reticulum autophagy (ER-phagy) in SIV-infected PAMs. RIG-I activator and p38 inhibitor reversed the upregulation of RETREG1 and AFB1-promoted SIV replication, and RETREG1 inhibitor reversed the AFB1-promoted SIV replication. In vivo experiments confirmed that AFB1 upregulated RETREG1 and p38, downregulated RIG-I, and promoted SIV replication and lung damage. Taken together, our results reveal that AFB1 promotes SIV replication and lung damage via RIG-I- and p38-mediated RETREG1/FAM134B-dependent ER-phagy and suggest the therapeutic potential of RETREG1-, RIG-I-, and p38-related drugs for influenza. Our findings also provide insights into why the occurrence of other infectious diseases is increasing.
Authors: Wenshuo Zhao, Siyao Pang, Jinlong Zhang, Zhaoran Yao, Yuqi Song, Yuhang Sun
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,650
OpenAlex ID: W4407964407