Environmental Molecular Sciences Laboratory

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Structure / Function Analysis of Positive-Strand RNA Virus Replication Complexes

Sunday, November 15, 2020
Principal Investigator: 
Paul Ahlquist
Lead Institution: 
University of Wisconsin, Madison
Project ID: 

SARS-CoV-2, Zika, Dengue, and many other dangerous viruses belong to the positive-strand RNA((+)RNA) viruses. Our group first used cryo-electron tomography (cryo-ET) to reveal the organization of viral RNA and protein components in membrane-bounded (+)RNA virus genome replication complexes. This included discovering a ringed “crown” complex of viral proteins guiding product RNA synthesis and release. A similar complex was just found in coronaviruses, highlighting conservation of RNA replication across (+)RNA viruses. Our recent 8.45 Å structure of the Nodavirus crown revealed that it is composed of 12 copies of multifunctional viral protein A with the viral RNA polymerase domain at the crown apex. We will now extend valuable preliminary results to map RNA capping and other domains in the crown, define dynamic conformational changes in crown assembly and function, and bridge cryo-ET to single particle imaging. The results should have fundamental implications for the function and control of many viruses