DRAM2 inhibits white spot syndrome virus infection via activating autophagy in Penaeus vannamei

Abstract

The DNA damage-regulated autophagy modulators have been identified as key activators of autophagy, an emerging mechanism to combat viral infections. In this study, we cloned and characterized the DNA damage-regulated autophagy modulator 2 homolog from the shrimp Penaeus vannamei (designated as PvDRAM2) and investigated its potential roles during white spot syndrome virus (WSSV) infection. The predicted three-dimensional structure of PvDRAM2 consists of six β-fold regions, which exhibit conservation with similar structures in other species. Phylogenetic analysis revealed that the clusters of PvDRAM2 evolved alongside invertebrate DRAMs, showing a close relationship with DRAMs from Penaeus japonicus and Homarus americanus. Quantitative real-time PCR (qRT-PCR) analysis indicated that PvDRAM2 is ubiquitously expressed across various shrimp tissues, with significantly increased expression levels in hemocytes and intestines following WSSV challenge. RNA interference (RNAi)-mediated knockdown of PvDRAM2 notably elevated WSSV loads and reduced survival rates in shrimps subjected to WSSV challenge. Functionally, the overexpression of PvDRAM2 enhanced autophagy in High Five cells. Additionally, the application of autophagy activators demonstrated that activating autophagy could counteract the increased WSSV replication precipitated by the knockdown of PvDRAM2. Collectively, our findings suggest that PvDRAM2 may inhibit WSSV infection by activating autophagy.