Carbohydrate metabolism is a determinant for the host specificity of baculovirus infections

Baculoviruses Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV) have highly similar genome sequences but exhibit no overlap in their host range. After baculovirus infects nonpermissive larvae (e.g., AcMNPV infecting B. mori or BmNPV infecting Spodoptera litura), we found that stored carbohydrates, including hemolymph trehalose and fat body glycogen, are rapidly transformed into glucose; enzymes involved in glycolysis and the TCA cycle are upregulated and produce more ATP; adenosine signaling that regulates glycolytic activity is also increased. Subsequently, phagocytosis in cellular immunity and the expression of genes involved in humoral immunity increase significantly. Moreover, inhibiting glycolysis and the expression of gloverins in nonpermissive hosts increased baculovirus infectivity, indicating that the stimulated energy production is designed to support the immune response against infection. Our study highlights that alteration of the host's carbohydrate metabolism is an important factor determining the host specificity of baculoviruses, in addition to viral factors.