Ervin Fodor

Molecular Mechanisms of RNA Virus Replication

Our laboratory focuses on elucidating the fundamental molecular mechanisms underlying the replication of RNA viruses such as Influenza, Nipah, and SARS-CoV-2. Specifically, we aim to uncover the structural and functional properties of the RNA polymerase of these viruses, as well as the mechanisms of transcription, replication and trafficking of the viral RNA genome. Our objective is to obtain in-depth molecular insights into the replication mechanisms of these RNA viruses, ultimately paving the way to the development of novel antiviral approaches.

Viruses with single-stranded RNA genomes represent a large group of viruses that includes numerous human, animal, and plant pathogens, such as influenza viruses, measles, rabies, Ebola, Nipah, Dengue, Zika, coronaviruses, and many others. A common feature of all these viruses is that they encode their RNA-dependent RNA polymerase, which is responsible for generating new copies of the viral genome through a complementary antigenome replicative intermediate. In the case of negative-sense RNA viruses, the RNA polymerase also transcribes the RNA genome into mRNA for the translation of viral proteins.

The primary focus of our laboratory is influenza viruses, which contain a segmented single-stranded negative-sense RNA genome. The RNA segments are assembled into viral ribonucleoprotein (vRNP) complexes, with the viral RNA polymerase bound to the partially complementary viral RNA termini, and the remaining part of the RNA bound to a scaffold of oligomeric viral nucleoprotein. It is in the context of these vRNPs that the RNA polymerase transcribes the RNA genome segments into mRNA and replicates them through a complementary RNA intermediate into new copies of the genome in the infected host cell nucleus.

We address questions ranging from how the influenza virus RNA polymerase switches between transcriptase and replicase functions in response to interactions with various host factors to how the RNA genome segments are exported from the nucleus and assembled into infectious progeny virus particles. We are also interested in uncovering the host range determinants of influenza viruses and understanding the effects of virus infection on the host cell, the molecular mechanisms of innate immune sensing, and host cell responses to viral infection.

We collaborate with structural biologists, physicists, chemists, and immunologists using an interdisciplinary approach that includes molecular and cell biology, structural biology (X-ray crystallography and cryo-electron microscopy), single-molecule and super-resolution microscopy, proteomics, and virology.

Group members

  • Ervin Fodor (Group leader)
  • Zihan Amanda Zhu (PhD student)
  • Stephanie Williams (PhD student)
  • Jack Whitehead (PhD student)
  • Fangzheng Wang (PhD student)
  • Ecco Staller (Postdoc)
  • Jane Sharps (Research assistant)
  • Alison Rep (PhD student)
  • Jeremy Keown (Visiting Postdoc from Strubi)
  • Franziska Günl (Postdoc)
  • Haitian Fan (Postdoc)
  • Kuang-Yu Chen (Postdoc)
  • Alaa Baazaoui (PhD student)

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