Integrated transcriptomic and metabolomic analysis reveals molecular mechanisms of infectious myonecrosis virus (IMNV) pathogenesis in Litopenaeus vannamei muscle tissue

The Infectious myonecrosis virus (IMNV) poses a significant threat to Litopenaeus vannamei, and there is limited research on the transcriptomic and metabolomic changes in shrimp muscle tissue post-infection. This study aims to integrate transcriptomic and metabolomic data to elucidate the gene expression and metabolic alterations in shrimp muscle tissue induced by IMNV. We present a molecular model of IMNV invasion and the mechanisms leading to muscle cell necrosis. Sequencing analyses at 30, 60, and 90 days post-infection identified 695, 2411, and 401 differentially expressed genes (DEGs) and 118, 131, and 68 significantly different metabolites (SDMs), respectively. In the early infection stage (IE, 30 days), we observed alterations in gene expression related to glucose and lipid metabolism, along with upregulation of antioxidant-related genes. The intermediate stage (IM, 60 days) exhibited significant reprogramming of metabolic pathways and signal transduction. In the persistent infection stage (IP, 90 days), we noted significant changes in energy metabolism and cell repair-related gene expression, with upregulation of genes involved in glycolysis and fatty acid biosynthesis to maintain energy supply.

Our proposed model for IMNV invasion encompasses viral receptor recognition, endosomal escape, replication, and maintenance of the host cell environment. IMNV binds to host cells via the laminin receptor (Lamr), with the SMPD1 gene facilitating endosomal escape through ceramide production. The PI3K-Akt-mTOR pathway provides energy for viral replication, while the JAK-STAT pathway may be hijacked by IMNV. The virus reprograms metabolism by regulating pathways and metabolites such as d-glucose-6-phosphate, D-aspartic acid, and L-glutamic acid, while enhancing autophagy and regulating sphingolipid metabolism and antioxidant mechanisms. During viral particle assembly and release, SMPD1 promotes necroptosis and ceramide production. Additionally, IMNV modulates cytoskeletal remodeling and adhesion by regulating the Act57B, Act5C, and Act88F genes. IMNV leads to host muscle cell necrosis by suppressing the immune response, inducing cytoskeletal remodeling, oxidative stress, and activating cell death pathways such as apoptosis and ferroptosis. These processes disrupt the structure and function of muscle cells, leading to extensive necrosis. This study provides insights into the pathogenic mechanisms of IMNV and establishes a foundation for the development of anti-IMNV strategies.