Bombyx mori UFBP1 regulates the IRE1α-SEC61α axis to facilitate BmNPV proliferation in silkworms

Haonan Meng; Xiuhong Zhou; Lixian Shu; Xiaochun Jiang; Muhammad Jalal; Cen Qian; Erkang Jiang; Chen Zhang; Shuyan Kong; Hualing Zhang; Shoujun Huang

doi:10.1016/j.ijbiomac.2025.145459

Bombyx mori UFBP1 regulates the IRE1α-SEC61α axis to facilitate BmNPV proliferation in silkworms

Int J Biol Macromol. 2025 Jun 22;319(Pt 2):145459. doi: 10.1016/j.ijbiomac.2025.145459. Online ahead of print.

Authors

Affiliations

¹ Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China.
² College of Chemistry and Life Sciences, Sichuan Provincial Key Laboratory for Development and Utilization of Characteristic Horticultural Biological Resources, Chengdu Normal University, Chengdu 611130, China.
³ Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei 230036, China. Electronic address: huangshoujun@ahau.edu.cn.

PMID: 40555317
DOI: 10.1016/j.ijbiomac.2025.145459

Abstract

The silkworm is a model organism for studying host-pathogen interactions, particularly with BmNPV, a major pathogen causing significant economic losses in sericulture. Here, we identified and functionally characterized the IRE1α-XBP1s signaling axis in silkworms. Knockdown of BmUFBP1, a key regulator of unfolded protein response, significantly reduced BmIRE1α and BmXBP1s expression, impairing the downstream target SEC61α and ultimately suppressing BmNPV proliferation. Inhibition of BmIRE1α promoted host cell apoptosis and reduced viral proliferation, while activation of BmIRE1α enhanced BmNPV proliferation. Furthermore, blocking the retro-translocation of misfolded proteins with Eeyarestatin I exacerbated ER stress and inhibited viral proliferation, whereas the chemical chaperone TUDC rescued viral proliferation in BmIRE1α-knockdown cells. These findings reveal that BmUFBP1 regulates BmNPV proliferation through the BmIRE1α-XBP1s axis, highlighting the critical role of ER protein homeostasis in viral proliferation. This study provides new insights into the molecular mechanisms of silkworm antiviral responses and offers potential strategies for enhancing BmNPV resistance in sericulture.

Keywords: Apoptosis; BmNPV; IRE1α; Unfolded protein response; XBP1.