Shrimp TM9SF4 facilitates WSSV infection probably through interacting with viral VP24 and regulating host autophagy

Autophagy is a highly conserved cellular process that plays a dual role during viral infection, contributing to antiviral defense while also being exploited by viruses to support their replication. However, the molecular mechanisms by which white spot syndrome virus (WSSV) influences host autophagy remain poorly understood. In this study, we identified LvTM9SF4, a phylogenetically conserved nine-transmembrane protein with predominantly expressed in the shrimp intestine, as a host factor that physically interacts with the WSSV structural protein VP24. Functional assays showed that RNAi-mediated knockdown of LvTM9SF4 significantly suppressed WSSV infection and enhanced shrimp survival after WSSV challenge in Pacific white shrimp (Litopenaeus vannamei). Subcellular localization analyses revealed substantial colocalization of LvTM9SF4 with the autophagy marker LC3B. Transcriptomic analysis further suggested that LvTM9SF4 knockdown affected autophagy-related pathways and genes, among which LvAtg2 exhibited the most substantial downregulation. Meanwhile, silencing LvAtg2 inhibited WSSV infection and improved shrimp survival, producing phenotypes similar to those observed following LvTM9SF4 knockdown. All the results indicated that LvTM9SF4 may participate in autophagy-related processes during WSSV infection, and that LvAtg2 may represent a potential downstream effector associated with this host-virus interaction. This study provides new insights into antiviral immunity in crustaceans and highlights potential host-targeted strategies against WSSV.