The compound packaged in virions is the key to trigger host glycolysis machinery for virus life cycle in the cytoplasm.

Viruses depend on the host metabolic machinery to complete their life cycle in the host cytoplasm. However, the key viral factors initiating the host machinery after the virus enters the cytoplasm remain unclear. Here, we found that compounds packaged in the virions of white spot syndrome virus, such as palmitic amide, could trigger the viral life cycle in the host cytoplasm. Palmitic amide promoted virus infection by enhancing host glycolysis by binding to triosephosphate isomerase to enhance its enzymatic activity. The glycolysis enhancement resulted in lactate accumulation, thereby promoting hypoxia-inducible factor 1 (HIF-1) expression. HIF-1 upregulation further enhanced glycolysis, which in turn promoted virus infection. Therefore, our study presented novel insight into the initiation of the virus life cycle in host cells.