Tudor staphylococcal nuclease promotes Bombyx mori cytoplasmic polyhedrosis virus replication through lipid metabolic reprogramming in silkworms.

Abstract

Bombyx mori cytoplasmic polyhedrosis virus (BmCPV), a double-stranded RNA reovirus, causes significant losses in sericulture; however, the host factors that support its replication remain poorly understood. Here, we identify Tudor staphylococcal nuclease (TSN) as a critical pro-viral host factor in silkworms. TSN is a multifunctional, evolutionarily conserved protein involved in transcription and RNA processing. BmTSN expression was increased markedly in BmCPV-infected midgut tissues. RNAi-mediated knockdown in BmN cells suppresses viral replication, whereas overexpression enhances it. Mechanistically, BmTSN drives a metabolic shift by enhancing lipid accumulation; knockdown of BmTSN reduces the expression of BmSREBP1 and other lipid-regulatory genes. Disruption of either BmTSN or BmSREBP1 reduces BmCPV replication. In a reciprocal effect, RNAi-mediated knockdown of BmSREBP1 also reduces BmTSN expression. Furthermore, BmSREBP1 transcriptionally activates BmTSN expression by binding to the BmTSN promoter, suggesting a regulatory loop between these factors. Together, these findings reveal a virus-induced BmTSN-BmSREBP1 axis that links host lipid metabolism to BmCPV replication. This work identifies BmTSN as a key host-dependency factor and provides new insights into virus-host interactions in insects.