Bombyx mori PAT4 gene inhibits BmNPV infection and replication through autophagy

Kaifang Jia; Jinyang Wang; Dan Jiang; Xiangrui Ding; Qiaoling Zhao; Dongxu Shen; Zhiyong Qiu; Xuelian Zhang; Cheng Lu; Heying Qian; Dingguo Xia

doi:10.1016/j.jip.2024.108235

Bombyx mori PAT4 gene inhibits BmNPV infection and replication through autophagy

J Invertebr Pathol. 2024 Nov 21:208:108235. doi: 10.1016/j.jip.2024.108235. Online ahead of print.

Authors

Affiliations

¹ Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Scientific Research Center, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China.
² Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture, Southwest University, Chongqing 400715, China.
³ Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, China; Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Scientific Research Center, Chinese Academy of Agricultural Sciences, Zhenjiang 212100, China. Electronic address: xiadingguo@126.com.

PMID: 39580048
DOI: 10.1016/j.jip.2024.108235

Abstract

Proton-assisted amino acid transporter 4 (PAT4) is a member of the solute carrier (SLC) 36 family, which mediates the transmembrane transport of amino acids and their derivatives. However, the function of PAT4 in Bombyx mori is not clear. In this study, BmPAT4 was cloned and identified using PCR technology. Its open reading frame (ORF) includes 1,395 bp, encoding 464 amino acid (Aa). Moreover, the sequence of BmPAT4 has the highest similarity with wild Bombyx.mandarina, Spodoptera frugiperda and Spodoptera litura, and it has ten transmembrane domains. BmPAT4 was localized in the cell membrane and expressed in all tissues of the silkworm. After Bombyx mori nuclear polyhedrosis virus (BmNPV) infection, the expression of BmPAT4 in midgut, hemolymph and fat body was significantly up-regulated. In addition, overexpression of BmPAT4 in BmN cells could significantly inhibit the proliferation of BmNPV, and the expression of several genes in autophagy pathway decreased significantly. On the contrary, down-regulation of BmPAT4 expression by RNA interference can promote BmNPV replication and proliferation, and the expression of key genes in autophagy pathway is significantly increased. This is the first time to report that BmPAT4 has an antiviral effect in silkworm. Moreover, the silkworm activates BmTORC1 via BmPAT4, which inhibits autophagy in silkworm cells, resulting in a lack of energy and raw materials for BmNPV infection and replication in cells.

Keywords: Antiviral; BmNPV; BmTORC1; Bombyx mori; Cellular autophagy; PAT4.