Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus Propagation

<i>Bombyx mori</i> nucleopolyhedrovirus (BmNPV) is a specific pathogen of <i>Bombyx mori</i> that can significantly impede agricultural development. Accumulating evidence indicates that the viral proliferation in the host requires an ample supply of energy. However, the corre...

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Main Authors: Miao Hu, Yi You, Yao Li, Shiyi Ma, Jiaqi Li, Meng Miao, Yanping Quan, Wei Yu
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/10/2084
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author Miao Hu
Yi You
Yao Li
Shiyi Ma
Jiaqi Li
Meng Miao
Yanping Quan
Wei Yu
author_facet Miao Hu
Yi You
Yao Li
Shiyi Ma
Jiaqi Li
Meng Miao
Yanping Quan
Wei Yu
author_sort Miao Hu
collection DOAJ
description <i>Bombyx mori</i> nucleopolyhedrovirus (BmNPV) is a specific pathogen of <i>Bombyx mori</i> that can significantly impede agricultural development. Accumulating evidence indicates that the viral proliferation in the host requires an ample supply of energy. However, the correlative reports of baculovirus are deficient, especially on the acetylation modification of tricarboxylic acid cycle (TCA cycle) metabolic enzymes. Our recent quantitative analysis of protein acetylome revealed that mitochondrial aconitase (ACO2) could be modified by (de)acetylation at lysine 56 (K56) during the BmNPV infection; however, the underlying mechanism is yet unknown. In order to understand this regulatory mechanism, the modification site K56 was mutated to arginine (Lys56Arg; K56R) to mimic deacetylated lysine. The results showed that mimic deacetylated mitochondrial ACO2 restricted enzymatic activity. Although the ATP production was enhanced after viral infection, K56 deacetylation of ACO2 suppressed BmN cellular ATP levels and mitochondrial membrane potential by affecting citrate synthase and isocitrate dehydrogenase activities compared with wild-type ACO2. Furthermore, the deacetylation of exogenous ACO2 lowered BmNPV replication and generation of progeny viruses. In summary, our study on ACO2 revealed the potential mechanism underlying WT ACO2 promotes the proliferation of BmNPV and K56 deacetylation of ACO2 eliminates this promotional effect, which might provide novel insights for developing antiviral strategies.
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spelling doaj.art-578a1cd90c0f4fa799a6e08b0270140f2023-11-19T18:28:03ZengMDPI AGViruses1999-49152023-10-011510208410.3390/v15102084Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus PropagationMiao Hu0Yi You1Yao Li2Shiyi Ma3Jiaqi Li4Meng Miao5Yanping Quan6Wei Yu7Institute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaInstitute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaInstitute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaInstitute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaInstitute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaInstitute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaInstitute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, ChinaInstitute of Biochemistry, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China<i>Bombyx mori</i> nucleopolyhedrovirus (BmNPV) is a specific pathogen of <i>Bombyx mori</i> that can significantly impede agricultural development. Accumulating evidence indicates that the viral proliferation in the host requires an ample supply of energy. However, the correlative reports of baculovirus are deficient, especially on the acetylation modification of tricarboxylic acid cycle (TCA cycle) metabolic enzymes. Our recent quantitative analysis of protein acetylome revealed that mitochondrial aconitase (ACO2) could be modified by (de)acetylation at lysine 56 (K56) during the BmNPV infection; however, the underlying mechanism is yet unknown. In order to understand this regulatory mechanism, the modification site K56 was mutated to arginine (Lys56Arg; K56R) to mimic deacetylated lysine. The results showed that mimic deacetylated mitochondrial ACO2 restricted enzymatic activity. Although the ATP production was enhanced after viral infection, K56 deacetylation of ACO2 suppressed BmN cellular ATP levels and mitochondrial membrane potential by affecting citrate synthase and isocitrate dehydrogenase activities compared with wild-type ACO2. Furthermore, the deacetylation of exogenous ACO2 lowered BmNPV replication and generation of progeny viruses. In summary, our study on ACO2 revealed the potential mechanism underlying WT ACO2 promotes the proliferation of BmNPV and K56 deacetylation of ACO2 eliminates this promotional effect, which might provide novel insights for developing antiviral strategies.https://www.mdpi.com/1999-4915/15/10/2084<i>Bombyx mori</i>BmNPVACO2deacetylationATP
spellingShingle Miao Hu
Yi You
Yao Li
Shiyi Ma
Jiaqi Li
Meng Miao
Yanping Quan
Wei Yu
Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus Propagation
Viruses
<i>Bombyx mori</i>
BmNPV
ACO2
deacetylation
ATP
title Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus Propagation
title_full Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus Propagation
title_fullStr Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus Propagation
title_full_unstemmed Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus Propagation
title_short Deacetylation of ACO2 Is Essential for Inhibiting <i>Bombyx mori</i> Nucleopolyhedrovirus Propagation
title_sort deacetylation of aco2 is essential for inhibiting i bombyx mori i nucleopolyhedrovirus propagation
topic <i>Bombyx mori</i>
BmNPV
ACO2
deacetylation
ATP
url https://www.mdpi.com/1999-4915/15/10/2084
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