Deacetylation of BmAda3 is required for cell apoptosis caused by Bombyx mori nucleopolyhedrovirus infection

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.

Bombyx mori transcription factor, E74A, beneficially affects BmNPV infection through direct interaction

“…For example, the mouse E74 promotes tumour proliferation by activating Mdm2 and inhibiting p53 expression 14 . In silkworms, the p53 gene has been shown to exert antiviral effects in BmNPV infection, 9 therefore we hypothesized that enhanced infection of BmNPV by BmE74A is associated with this pathway. To test this hypothesis, the expressions of BmMdm2 and Bmp53 after the knockdown and overexpression of BmE74A were measured, and the role of BmE74A was indicated by a significant decrease in the expression of BmMdm2 and an increase in the expression of Bmp53 after BmE74A knockdown, which was also validated after BmE74A overexpression (Figs 3 and 5).…”

“…1 The second is the inhibition of viral infections, for example BmAda3 deacetylation can reduce BmNPV proliferation by enhancing the stability of TF p53 and promoting host cell apoptosis. 9 By contrast, BmFoxO increases the transcriptional activity of the BmPEPCK-2 promoter by inhibiting the proliferation of BmNPV. 10 E74 belongs to the erythroblast transformation-specific (ETS) family of TFs and functions as a transcriptional activator or repressor in the cell cycle and in physiological development, [11][12][13] and has been widely reported in the occurrence and development of tumours and cancers.…”

“…The first is the promotion of viral proliferations, for example TF Bm11 is involved in producing occlusion bodies (OB) and occlusion‐derived virus (ODV) embedding, which aid BmNPV infection 1 . The second is the inhibition of viral infections, for example BmAda3 deacetylation can reduce BmNPV proliferation by enhancing the stability of TF p53 and promoting host cell apoptosis 9 . By contrast, BmFoxO increases the transcriptional activity of the BmPEPCK‐2 promoter by inhibiting the proliferation of BmNPV 10 …”

Progress on innate immune evasion and live attenuated vaccine of pseudorabies virus

“…Apoptosis is a programmed cell death characterized by blistering of the cell membrane, chromatin condensation, and DNA fragmentation while maintaining membrane integrity to form apoptotic vesicles (Arandjelovic and Ravichandran, 2015). Apoptosis is a means of host resistance to pathogen invasion, causing premature death of infected cells resulting in abortion of viral proliferation and induction of specific immunity by mildly releasing antigens (Koyama et al, 2000;Zhu et al, 2021). PRV induced-apoptosis has been reported (Cheung et al, 2000;Aleman et al, 2001).…”

Deacetylation of ACO2 Is Essential for Inhibiting Bombyx mori Nucleopolyhedrovirus Propagation

“…As a model insect for genetics and immunology research [ 2 ], the insect is susceptible to Bombyx mori nucleopolyhedrovirus (BmNPV), which causes severe economic losses in sericulture [ 3 ]. BmNPV is a baculovirus that specifically infects silkworms and has a large circular double-stranded DNA genome with 143 putative open reading frames [ 4 ]. Silkworms and BmNPV constitute a well-established model of insect–virus interactions, including host immune response and immune escape from a virus.…”