【105 Ta-You Wu Memorial Award】Special Issue
In his book Managing in the Next Society (2002), Peter F. Drucker predicted that “biotechnology and aquaculture will be important industries in this new century”. In the last decade, it has also become increasingly clear that these sectors represent a potential solution to the global food crisis. Today, shrimp aquaculture is a global industry that flourishes in Asia, America and Africa. However, this industry is currently threatened by a number of serious shrimp diseases. In addition to AHPND (Acute Hepatopancreatic Necrosis Disease), which is caused by Vibrio parahaemolyticus, there is also shrimp WSD (white spot disease), which originally swept through the shrimp aquaculture industry with devastating effect in 1995. This disease is caused by the shrimp virus WSSV (white spot syndrome virus). WSSV continues to cause severe economic losses, and the shrimp industry continues to seek an effective strategy against this disease. The mechanisms of shrimp-WSSV interactions therefore urgently need to be characterized. However, studies on shrimp and WSSV have been limited by the following:
(1) Shrimp is not a model organism; therefore, the global public database is limited and most studies take a long time. Moreover, the lack of shrimp cell lines is also problematic.
(2) WSSV is a large circular DNA virus. Among 532 ORFs that can be transcribed, more than 90% are novel proteins show no sequence homology with any entries in current databases. Therefore, most studies have concentrated on the analysis of a few virus particle structural proteins, whereas the overall picture of WSSV pathogenesis has not been adequately established.
Research is essential to help the aquaculture industry become environmentally friendly and sustainable, and as an associate professor at NCKU, I am currently the principal investigator of five academic research teams from NCKU, NTU and Academia Sinica. All five teams have cooperated closely to focus on the global interactions between shrimp and WSSV and to characterize WSSV pathogenesis. By starting from a basic research question, and subsequently using genomics, proteomics, metabolomics and other systems biological strategies, we have successfully characterized the key host mechanisms for virus replication. Using an in vivo model, we have found that WSSV completes its replication cycle by triggering the cancer-cell-like Warburg effect (i.e. aerobic glycolysis), glutaminolysis and lipid metabolism. Our coordinated studies were the first to show that an invertebrate virus (WSSV) can trigger the Warburg effect in an invertebrate (white shrimp). Notably, we found that if we blocked these effects, WSSV replication was inhibited, and the infected animal did not develop the disease. It was also determined that the mTORC2 pathway was essential for triggering the above WSSV-induced metabolic changes. In addition, when the Warburg effect was suppressed by pretreatment with the mTOR inhibitor Torin 1, even the subsequent up-regulation of the TCA cycle was insufficient to satisfy the virus’s requirements for energy and macromolecular precursors. We concluded that these factors could be applied in the future selection of disease-resistant shrimp.