Abstract
Simple SummaryBaculoviruses arrest the cell cycle in the S or G2/M phase in insect cells, but the exact mechanism of this process still remains obscure. Bombyx mori nucleopolyhedrovirus (BmNPV), one of the best characterized baculoviruses, is an important pathogen in silkworms. In the present study, we determined that downregulation of BmCDK1 and BmCyclin B expression was required for BmNPV-mediated G2/M phase arrest, which plays an essential role in facilitating BmNPV replication. Further investigations showed that BmNPV IAP1 interacted with BmCDK1. The overexpression of the BmNPV iap1 gene led to the accumulation of cells in the G2/M phase, and BmNPV iap1 gene knockdown attenuated the effect of BmNPV-mediated G2/M phase arrest. These findings enhance the understanding of BmNPV pathogenesis, and indicate a novel mechanism through which baculoviruses impact the cell cycle progression.Understanding virus–host interaction is very important for delineating the mechanism involved in viral replication and host resistance. Baculovirus, an insect virus, can cause S or G2/M phase arrest in insect cells. However, the roles and mechanism of Baculovirus-mediated S or G2/M phase arrest are not fully understood. Our results, obtained using flow cytometry (FCM), tubulin-labeling, BrdU-labeling, and CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS), showed that Bombyx mori nucleopolyhedrovirus (BmNPV) induced G2/M phase arrest and inhibited cellular DNA replication as well as cell proliferation in BmN-SWU1 cells. We found that BmNPV induced G2/M arrest to support its replication and proliferation by reducing the expression of BmCDK1 and BmCyclin B. Co-immunoprecipitation assays confirmed that BmNPV IAP1 interacted with BmCDK1. BmNPV iap1 was involved in the process of BmNPV-induced G2/M arrest by reducing the content of BmCDK1. Taken together, our results improve the understanding of the virus–host interaction network, and provide a potential target gene that connects apoptosis and the cell cycle.
Highlights
Viruses are obligate intracellular parasites, and usually utilize proteins and enzymes encoded by host for their multiplication
We demonstrated that Bombyx mori nucleopolyhedrovirus (BmNPV) IAP1 interacted with BmCDK1, and that BmNPV iap1 was involved in G2/M arrest
The change in cell cycle was first assessed in BmNPV-infected BmN-SWU1 cells
Summary
Viruses are obligate intracellular parasites, and usually utilize proteins and enzymes encoded by host for their multiplication. The Cyclin B-CDK1 complexes, known as MPF (mitosis promoting factor), play key roles in controlling G2 progression and M phase entry [17,18]. Viruses interfere with the cell cycle progression largely by deregulating cell cycle checkpoints at multiple levels of gene expression, including transcription, post-transcriptional processing, translation, post-translational modification, and protein stabilization [23]. Interactions between viral proteins and cyclins or CDKs (cyclin-dependent kinases, CDKs) affect the activity, expression levels, and redistribution of cyclins or CDKs [24,25,26,27]. Some viruses (e.g., Herpesvirus saimiri) encode cell cycle-related proteins to antagonize cell cycle checkpoints [28,29,30,31]. Cell cycle arrest is complicated, and the mechanism by which viruses manipulate the cell cycle progression still requires exploration
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