Deacetylation of BmAda3 is required for cell apoptosis caused by Bombyx mori nucleopolyhedrovirus infection. Issue 2 (4th August 2021)

• Record Type: Journal Article
• Authors: Zhu, Yajie; Hu, Miao; Ngowo, Jonas; Gao, Xu; Chen, Xi; Yan, Huihui; Yu, Wei
• Is Part Of: Archives of insect biochemistry and physiology. Volume 108:Issue 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-04
• Subjects: apoptosis -- BmNPV -- BmAda3 -- deacetylation -- P53 stability; Insects -- Physiology -- Periodicals; Insect biochemistry -- Periodicals; 595.701572
• DOI: 10.1002/arch.21838
• Languages: English
• ISSNs: 0739-4462

Abstract

Abstract: 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. Research highlights: Deacetylation of BmAda3 K124/K128 stabilized the apoptosis‐promoting factor P53. Deacetylation of BmAda3 K124/K128 promoted apoptosis of host cells infected by BmNPV. Deacetylation of BmAda3 K124/K128 was detrimental to the proliferation of BmNPV. Abstract : K124/K128 deacetylation of BmAda3 could stabilize the P53 protein, thereby reducing the proliferation of the virus by promoting the host cell apoptosis.