Active Genetics & Molecular Biology Cells, Biochemistry & Physiology

Replication and Assembly of Influenza virus

Funder Wellcome Charity-funded
Recipient organisation University of Oxford
Funding £1.6M
Period Sept 2022 — Aug 2027

In plain English

AI plain-English summary

Influenza viruses hijack a cell’s nucleus to copy their eight RNA segments, then smuggle them out to the cell membrane to build new viruses. The core machinery—a polymerase bound to each RNA segment and wrapped in N protein—has been imaged at atomic scale, but the steps between copying and assembly remain a black box. This project will use a combination of X-ray crystallography, cryo-electron microscopy, and high-resolution cellular imaging to track how newly made viral ribonucleoproteins (vRNPs) are produced, exported from the nucleus, and finally packed into budding viruses. If successful, the work will reveal the molecular choreography of influenza’s assembly line, identifying structural weak points that drugs could target. This is fundamental science: there is no immediate clinical application. But understanding how influenza coordinates replication and assembly at atomic resolution could eventually inform the design of antivirals that block nuclear export or disrupt packaging—steps essential for the virus to spread. Past fundamental work on viral polymerases, for example, directly enabled the development of current influenza drugs such as oseltamivir.

View original technical description
The theme of the proposed research is our understanding of the replication and assembly of Influenza virus, from a structural imaging perspective. The transcription and replication of the influenza virus genome occurs in the nucleus and the structure of the isolated polymerase reveals at a molecular level key steps in transcription and replication. The genome of Influenza virus is composed of 8 RNA segments each bound to the viral RNA polymerase and multiple copies of N protein to form ribonucleoprotein complexes (vRNPs). Newly replicated vRNPs are transported out of the nucleus, where they are trafficked to the cell membrane and assemble to form new viruses budding out from the cell membrane. How the production and assembly of RNPs is coordinated in the nucleus and the details of how the vRNPs are transported out of the nucleus to the cell membrane is unknown. By integrating structural, biochemical and cellular imaging, I aim to understand with atomic-level detail, vRNP production, nuclear export and viral assembly. This will be done using crystallography and single particle cryo-EM, combined with high resolution cellular EM and X-ray tomography, correlated with cryo- fluorescence imaging of infected cells to understand these key stages in the viral cycle.

View the original record at the funder ↗

Researchers

Jonathan Grimes (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

A mechanistic understanding of the replication of Influenza Virus
Visualising influenza virus RNA replication
Investigating Viral Genome Replication and Assembly Using Cryo Electron Microscopy
Molecular interactions between the transcriptional machinery of influenza virus and the host cell
Transcription, replication, trafficking and assembly of the influenza virus RNA genome

Original classification

Investigator Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.