# Deacetylation of BmHSP90 at Lysines 550/567 Stimulates Its Chaperone Function and Actin Polymerization to Drive the Proliferation of Bombyx mori Nucleopolyhedrovirus

## TL;DR

This study shows that deacetylation of BmHSP90 helps the BmNPV virus replicate in silkworm cells, offering a new target for antiviral strategies in sericulture.

## Contribution

The study identifies deacetylation of BmHSP90 at lysines 550/567 as a novel mechanism supporting BmNPV proliferation.

## Key findings

- Deacetylation of BmHSP90 at K550 and K567 enhances its dimerization and chaperone activity.
- The deacetylated BmHSP90 promotes actin polymerization and BmNPV replication.
- BmNPV exploits BmHSP90 deacetylation to support its proliferation in host cells.

## Abstract

Heat shock protein 90 (HSP90) is a highly conserved chaperone that facilitates the proliferation of many viruses, including Bombyx mori nucleopolyhedrovirus (BmNPV), but the underlying regulatory mechanism is unclear. In Bombyx mori ovary cells infected with BmNPV, we previously observed a significant reduction in the acetylation levels of Bombyx mori HSP90 (BmHSP90) at lysines 550 and 567. To clarify the function of two deacetylation sites, we introduced point mutations to generate an acetylation-deficient (lysine to arginine) mutant of BmHSP90 at lysines 550 and 567. The deacetylation-mimetic mutation enhanced BmHSP90’s homodimerization and chaperone activity, strengthened its actin interaction to promote nuclear polymerization, and promoted BmNPV replication, viral gene transcription, and progeny production. We conclude that BmNPV hijacks BmHSP90 deacetylation to support its proliferation. This work highlights BmHSP90 CTD acetylation as a potential antiviral target, aiding pest control in sericulture.

The silkworm, Bombyx mori, is a model organism with significant agricultural and economic importance, but it is threatened by Bombyx mori nucleopolyhedrovirus (BmNPV). A crucial chaperone, heat shock protein 90 (HSP90), can also facilitate the proliferation of viruses, and our previous quantitative acetylome analysis revealed that lysines 550 and 567 in the carboxyl-terminal domain (CTD) of Bombyx mori HSP90 (BmHSP90) were significantly deacetylated following BmNPV infection, but the underlying mechanism remained unknown. In this study, deacetylation-mimetic (K to R) mutants of BmHSP90 exhibited increased dimerization and chaperone activity compared with the wild-type. In addition, the mutants also exhibited higher affinity for actin, promoting F-actin polymerization. Collectively, these changes facilitated BmNPV replication and progeny virion production. This study reveals that the deacetylation of BmHSP90 at K550 and K567 mediates crucial host–virus interactions, providing novel insights into potential antiviral strategies.