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ORF603 derived from AcMNPV plays entirely opposite roles in regulating BmNPV infection
Xin-Yi Ding1, Jiang-Zhi Su1, Yu-Shuo Song1
1Jiangsu Key Laboratory of Sericultural and Animal Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang 212100, Jiangsu, China.
Abstract:
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV) exhibit high genomic similarity but display significant differences in host range. The identification of key genes associated with this difference is of great importance for expanding its application in pest biocontrol. Fifteen genes specific to AcMNPV were identified. Among the constructed recombinant BmNPV, only ORF603 altered the virulence of BmNPV. Interestingly, our findings reveal a biological phenomenon that contradicts the prevailing theoretical framework. Current theory posits a positive correlation between viral virulence and replication efficiency; however, we observed that the recombinant virus vBmNPV-ORF603 exhibited high virulence despite significantly inhibited viral DNA replication. Furthermore, ORF603 exhibits entirely opposing roles during infections by AcMNPV and BmNPV. The underlying mechanism was determined to involve ORF603-induced G2/M phase cell cycle arrest in BmN cells, which consequently suppressed viral DNA replication. Meanwhile, the significant upregulation of genes associated with ribosome biogenesis and autophagy enhanced the transcription and translation efficiency of viral genes, thereby facilitating viral proliferation and intensifying the infection. The results demonstrate that the ORF603 of AcMNPV mediates a trade-off between viral virulence and transmission capacity in BmNPV. This functional dichotomy offers novel insights into the regulation of infection strategies in baculoviruses and highlights potential targets for engineering enhanced viral biopesticides.
Insights
Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ORF603 enhances Bombyx mori nucleopolyhedrovirus (BmNPV) virulence by inhibiting DNA replication. This baculovirus gene offers insights for developing improved biopesticides.
Area of Science:
- Virology
- Molecular Biology
- Pest Management
Background:
- Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV) share genomic similarity but differ in host range.
- Identifying genes responsible for host specificity is crucial for expanding baculovirus applications in biocontrol.
Purpose of the Study:
- To identify genes in AcMNPV responsible for host range differences.
- To investigate the role of specific AcMNPV genes, particularly ORF603, in altering BmNPV virulence and replication.
- To elucidate the molecular mechanisms underlying the observed effects of ORF603 on viral infection strategies.
Main Methods:
- Construction and analysis of recombinant BmNPV expressing AcMNPV-specific genes.
- Assessment of viral virulence and DNA replication efficiency in recombinant viruses.
- Investigation of host cell responses, including cell cycle arrest and gene expression related to ribosome biogenesis and autophagy.
Main Results:
- Fifteen AcMNPV-specific genes were identified; only ORF603 significantly altered BmNPV virulence.
- Recombinant vBmNPV-ORF603 exhibited high virulence despite suppressed viral DNA replication, contradicting established theories.
- ORF603 induced G2/M cell cycle arrest in BmN cells, inhibiting DNA replication while enhancing viral gene transcription/translation via ribosome and autophagy pathways.
Conclusions:
- AcMNPV ORF603 plays a dual role, mediating a trade-off between virulence and transmission in BmNPV.
- The findings provide novel insights into baculovirus infection regulation and host-pathogen interactions.
- ORF603 represents a potential target for engineering enhanced viral biopesticides with tailored virulence and transmission characteristics.
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