K64 acetylation of heat shock protein 90 suppresses nucleopolyhedrovirus replication in Bombyx mori

HSP90 is a highly conserved chaperone that facilitates the proliferation of many viruses, including silkworm (bombyx mori) nucleopolyhedrovirus (BmNPV), but the underlying regulatory mechanism was unclear. We found that suppression of HSP90 by 17-AAG, a HSP90-specific inhibitor, significantly reduced the expression of BmNPV capsid protein gp64 and viral genome replication, whereas overexpression of B. mori HSP90(BmHSP90) promoted BmNPV replication. Furthermore, in a recent study of the lysine acetylome of B. mori infected with BmNPV, we focused on the reduced viral proliferation due to changes of BmHSP90 lysine acetylation. Site-directed introduction of acetylated (K/Q) or deacetylated (K/R) mimic mutations into BmHSP90 revealed that lysine 64 (K64) acetylation activated the JAK/STAT pathway and reduced BmHSP90 ATPase activity, leading to diminished chaperone activity and ultimately inhibiting BmNPV proliferation. In this study, a single lysine 64 acetylation change of BmHSP90 was elucidated as a model of posttranslational modifications occurring in the wake of host-virus interactions, providing novel insights into potential antiviral strategies.