WSSV exploits host glycolytic reprogramming to promote hemocyanin lactylation and enhance cell-associated WSSV levels in shrimp.

Abstract

White spot syndrome virus (WSSV) is a major pathogen in shrimp aquaculture, yet how virus-induced metabolic rewiring alters immune effector function remains poorly understood. Here, we show that WSSV infection in Litopenaeus vannamei induces a Warburg-like metabolic shift characterized by increased glucose uptake, transcriptional activation of glycolytic genes, lactate accumulation, and reduced acetyl-CoA levels. This metabolic state is accompanied by enhanced lactylation and reduced acetylation of hemocyanin, a major respiratory and immune protein in shrimp. Through transcriptome-guided candidate screening and in vivo RNA interference, we identify Tip60 as a positive regulator of hemocyanin lactylation, whereas HDAC3 and SIRT2 act as negative regulators. Functional assays further demonstrate that hemocyanin samples isolated from sodium L-lactate-injected shrimp exhibit enhanced capacities to increase cell-associated WSSV on hemocytes and promote viral proliferation. Together, these findings support a model in which WSSV hijacks host glycolytic reprogramming to reshape the post-translational modification landscape and convert hemocyanin into a proviral factor. This study establishes a non-histone lactylation mechanism in crustacean antiviral biology and identifies the Tip60/HDAC3/SIRT2 axis as a potential target for host-directed control of WSSV infection.