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Summary
Human norovirus RNA-dependent RNA polymerase forms liquid-liquid phase-separated condensates that serve as viral replication factories, providing a potential target for antiviral therapy.
Highlights
- HuNoV RdRp forms liquid-liquid phase-separated condensates.
- These condensates serve as viral replication factories.
- The condensates are dynamic and allow for the exchange of molecules.
- The formation of condensates is modulated by pH, salt concentration, and molecular crowding.
- The flexible N-terminal region of RdRp is critical for LLPS.
- RdRp is enzymatically active within the condensates.
- The condensates are associated with markers for Golgi and ER.
Key Insights
- The study reveals a previously unknown property of HuNoV RdRp in forming biomolecular condensates as platforms for genome replication.
- The formation of phase-separated condensates as replication hubs may be a necessary mechanism in positive-sense RNA viruses to effectively segregate the otherwise conflicting translation and replication events.
- The liquid-to-solid transition of the condensates may provide a mechanism to regulate viral replication.
- The association of RdRp condensates with membrane markers suggests that HuNoVs recruit membranes derived from late compartments within the secretory pathway with some specificity.
- The study opens new targets for designing antivirals for HuNoV infections, which remains a serious threat in children and immunocompromised patients.
- The findings have implications for understanding the replication mechanisms of other positive-sense RNA viruses.
- The study highlights the importance of considering the role of biomolecular condensates in viral replication and the potential for targeting these condensates in antiviral therapy.
Mindmap
Citation
Kaundal, S., Anish, R., Ayyar, B. V., Shanker, S., Kaur, G., Crawford, S. E., Pollet, J., Stossi, F., Estes, M. K., & Prasad, B. V. V. (2024). RNA-dependent RNA polymerase of predominant human norovirus forms liquid-liquid phase condensates as viral replication factories. In Science Advances (Vol. 10, Issue 51). American Association for the Advancement of Science (AAAS). https://doi.org/10.1126/sciadv.adp9333