Oligomerization of Baculovirus LEF-11 Is Involved in Viral DNA Replication

Dong, Zhanqi; Hu, Nan; Zhang, Jun; Chen, Tingting; Cao, Mengji; Li, Haiqing; Lei, Xue-jiao; Chen, Peng; Lü, Cheng; Pan, Min‐Hui

doi:10.1371/journal.pone.0144930

Cited by 20 publications

(22 citation statements)

References 30 publications

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“…In the present study, our research revealed that knockdown of ATAD3A, HSPD1 and LEF-11 significantly reduced the protein expression and DNA replication of the virus (Fig. 4)23. This indicated that the ATAD3A and HSPD1 are required for the efficient multiplication of BmNPV.…”

Section: Discussionsupporting

confidence: 64%

“…Following viral entry of host cells, immediate early gene expression and viral initiation DNA replication occurs2341. After initiating DNA replication of baculovirus, the LEF-11 protein was expressed and hijack host ATPase family members ATAD3A and HSPD139.…”

Section: Discussionmentioning

confidence: 99%

“…We further identified that LEF-11 contains a nuclear localization signal and localizes to viral DNA replication sites in BmNPV infection cells27. Additionally, those results showed that the baculovirus LEF-11 and its oligomerization domains were required for viral DNA replication23. Although various studies have demonstrated that LEF-11 plays an important role in viral DNA replication, the cellular mechanisms of LEF-11 regulation are largely unknown.…”

mentioning

confidence: 83%

“…Baculovirus lef-11 gene encodes a putative protein with molecular mass of 13.1 KDa26. In our previous study, we indicated that Bombyx mori nucleopolyhedrovirus (BmNPV) LEF-11 is conserved in all 63 sequenced baculovirus genomes except Diptera CuniNPV23. We further identified that LEF-11 contains a nuclear localization signal and localizes to viral DNA replication sites in BmNPV infection cells27.…”

mentioning

confidence: 98%

“…Baculovirus late expression factors (LEFs) are involved in viral DNA replication and viral gene regulation232425. Baculovirus lef-11 gene encodes a putative protein with molecular mass of 13.1 KDa26.…”

mentioning

confidence: 99%

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Baculovirus LEF-11 Hijack Host ATPase ATAD3A to Promote Virus Multiplication in Bombyx mori cells

Dong

et al. 2017

Sci Rep

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Research on molecular mechanisms that viruses use to regulate the host apparatus is important in virus infection control and antiviral therapy exploration. Our previous research showed that the Bombyx mori nucleopolyhedrovirus (BmNPV) LEF-11 localized to dense regions of the cell nucleus and is required for viral DNA replication. Herein, we examined the mechanism of LEF-11 on BmNPV multiplication and demonstrated that baculovirus LEF-11 interacts with Bombyx mori ATAD3A and HSPD1 (HSP60) protein. Furthermore, we showed that LEF-11 has the ability to induce and up-regulate the expression of ATAD3A and HSPD1, phenomena that were both reversed upon knockdown of lef-11. Our findings showed that ATAD3A and HSPD1 were necessary and contributed to BmNPV multiplication in Bombyx mori cells. Moreover, ATAD3A was found to directly interact with HSPD1. Interestingly, ATAD3A was required for the expression of HSPD1, while the knockdown of HSPD1 had no obvious effect on the expression level of ATAD3A. Taken together, the data presented in the current study demonstrated that baculovirus LEF-11 hijacks the host ATPase family members, ATAD3A and HSPD1, efficiently promote the multiplication of the virus. This study furthers our understanding of how baculovirus modulates energy metabolism of the host and provides a new insight into the molecular mechanisms of antiviral research.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 83%

mentioning

confidence: 98%

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confidence: 99%

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Baculovirus LEF-11 Hijack Host ATPase ATAD3A to Promote Virus Multiplication in Bombyx mori cells

Dong

et al. 2017

Sci Rep

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Establishment of a baculovirus-inducible CRISPR/Cas9 system for antiviral research in transgenic silkworms

Dong

Huang

Dong

et al. 2018

Appl Microbiol Biotechnol

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The CRISPR/Cas9 system is a powerful genetic engineering technique that has been widely used in gene therapy, as well as in the development of novel antimicrobials and transgenic insects. However, several challenges, including the lack of effective host target genes and the off-target effects, limit the application of CRISPR/Cas9 in insects. To mitigate these difficulties, we established a highly efficient virus-inducible CRISPR/Cas9 system in transgenic silkworms. This system includes the baculovirus-inducible promoter 39K, which directs transcription of the gene encoding, the Cas9 protein, and the U6 promoter which targets the sgATAD3A site of the ATPase family AAA domain-containing protein 3 (ATAD3A) gene. The double-positive transgenic line sgATAD3A×39K-Cas9 (ATAD3A-KO) was obtained by hybridization; antiviral activity in this hybrid transgenic line is induced only after Bombyx mori nucleopolyhedrovirus (BmNPV) infection. The BmNPV-inducible system significantly reduced off-target effects and did not affect the economically important characteristics of the transgenic silkworms. Most importantly, this novel system efficiently and consistently edited target genes, inhibiting BmNPV replication after the transgenic silkworms were inoculated with occlusion bodies (OBs). The suppression of BmNPV by the virus-inducible system was comparable to that of the stably expressed CRISPR/Cas9 system. Therefore, we successfully established a highly efficient BmNPV-inducible ATAD3A-KO transgenic silkworm line, with improved gene targeting specificity and antiviral efficiency. Our study thereby provides insights into the treatment of infectious diseases and into the control of insect pests.

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A novel system to rapidly detect protein–protein interactions (PPIs) based on fluorescence co-localization

Dong

Chen

et al. 2020

Biotechnol Lett

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Oligomerization of Baculovirus LEF-11 Is Involved in Viral DNA Replication

Cited by 20 publications

References 30 publications

Baculovirus LEF-11 Hijack Host ATPase ATAD3A to Promote Virus Multiplication in Bombyx mori cells

Baculovirus LEF-11 Hijack Host ATPase ATAD3A to Promote Virus Multiplication in Bombyx mori cells

Establishment of a baculovirus-inducible CRISPR/Cas9 system for antiviral research in transgenic silkworms

A novel system to rapidly detect protein–protein interactions (PPIs) based on fluorescence co-localization

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