Silkworm (Bombyx mori) is a model organism with great agricultural economic value that plays a crucial role in biological studies. B. mori nucleopolyhedrovirus (BmNPV) is a major viral pathogen found in silkworms, which leads to huge silk loss annually. In a recent lysine acetylome of silkworm infected with BmNPV, we focused on the heat shock cognate protein 70-4 (HSC70-4) lysine acetylation change due to the consequent nuclear accumulation and viral structure assembly. In this study, the genome replication, proliferation, and production of budded viruses (BVs) were arrested by HSP/HSC70 inhibitor treatment. However, HSC70-4 overexpression enhanced BmNPV reproduction. Furthermore, site-direct mutagenesis for acetylated mimic (K/Q) or deacetylated mimic (K/R) mutants of HSC70-4 demonstrated that lysine 77 (K77) deacetylation promotes HSC70-4 stability, viral DNA duplication, and HSC70-4 nuclear entry upon BmNPV challenge, and the nuclear propulsion of HSC70-4 after viral stimulus might be dependent on the interaction with the carboxyl terminus of HSC70-interacting protein (CHIP, an E3 ubiquitin ligase), followed by ubiquitin-proteasome system assistance. In this study, single lysine 77 deacetylation of HSC70-4 was deemed a part of the locomotive pathway for facilitating BmNPV proliferation and provided novel insights into the antiviral strategic development.
Silkworm is not only an ideal insect model with a biological significance, but it is also crucially important in sericulture and bioreactors. Bombyx mori nucleopolyhedrovirus (BmNPV) is a principal pathogen of silkworm. However, the molecular mechanism underlying BmNPV invasion is still unclear. Based on our previous acetylome research findings of B. mori after BmNPV infection, here, we focused on silkworm alteration/deficiency in activation‐3 (BmAda3). The acetylation of K124 and K128 were significantly reduced (0.66‐fold) upon the virus challenge. Due to the interaction between Ada3 and P53, acetylation‐mimic K124Q/K128Q and deacetylation‐mimic K124R/K128R mutants of BmAda3 were constructed to explore the roles exerted by the acetylation modification of BmAda3 on P53. Yeast two‐hybrid and IP results revealed that both BmAda3 and its deacetylation mutants (K124R/K128R) interacted with P53. Interestingly, we found that the deacetylation mutants (K124R/K128R) of BmAda3 significantly promoted the stability of P53. Since P53 is a proapoptotic factor, cell apoptosis was detected. We established that the deacetylation of BmAda3 at K124/K128 facilitated cellular apoptosis during BmNPV infection. Finally, viral proliferation was analyzed, and the results indicated that virus generation was reduced by K124/K128 deacetylation. Our report, based on the deacetylation of two lysine sites 124/128 of BmAda3, shows possible regulatory pathways of BmNPV proliferation and provides novel insights into the development of antiviral agents.
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