During the complex processes of virus replication and transmission, host cells play a crucial role, especially through the formation of biomolecular condensates (BMCs). These membraneless subcellular compartments have emerged as key organizers and regulators of viral processes.
Nevertheless, understanding how viruses leverage host factors to orchestrate BMCs formation and harnessing this process for antiviral drug development continues to be a challenging yet promising field of study.
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Recently, researchers from the State Key Laboratory of Green Pesticides at Guizhou University made a groundbreaking discovery in their study of the Cucumber Green Mottle Mosaic Virus (CGMMV). They revealed that CGMMV cleverly utilizes the host cytosolic fructose-1,6-bisphosphatase (FBPase) to catalyze the formation of BMCs via liquid-liquid phase separation (LLPS).
Mechanism of BMC formation
The capsid protein of CGMMV (CGMMV-CP) interacts specifically with cytosolic FBPase (NbFBPase) in host cells. This interaction results in the formation of BMCs through LLPS, creating a conducive microenvironment for CGMMV replication and particle assembly.
Overexpression of NbFBPase promotes CGMMV proliferation, whereas silencing it inhibits viral replication, further emphasizing the pivotal role of NbFBPase in this process.
Further investigation revealed that Tyr18, an amino acid residue within CGMMV-CP, is crucial for viral pathogenicity, virion assembly, and BMC formation. Compound C1, a novel benzo[d]oxazol derivative, was designed and synthesized, demonstrating remarkable inhibitory activity against CGMMV, surpassing the efficacy of existing antiviral drugs like Ningnanmycin. Compound C1 targets Tyr18, disrupting the formation of condensates and effectively inhibiting viral replication.
Impact on host photosynthesis
Transcriptome analysis showed that Tyr18 regulates the expression of the Calvin cycle-related gene glpX-SEBP in host cells, impacting photosynthesis. This finding suggests a potential mechanism by which CGMMV optimizes its replication and pathogenicity by reshaping host photosynthetic pathways.
The research team also discovered interactions between CGMMV-CP and homologs of FBPase from other cucurbitaceae plants, like cucumber and melon, further underscoring the central role of Tyr18 in the virus-host interaction network.
This study not only provides insights into CGMMV-host interactions but also paves the way for designing targeted antiviral drugs against CGMMV and potentially other viruses.
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