Viral Infections Exacerbate FUS-ALS Phenotypes in iPSC-Derived Spinal Neurons in a Virus Species-Specific Manner

Research output: Contribution to journalResearch articleContributedpeer-review


  • Jessica Bellmann - , TUD Dresden University of Technology (Author)
  • Anne Monette - , McGill University (Author)
  • Vadreenath Tripathy - , TUD Dresden University of Technology (Author)
  • Anna Sójka - , TUD Dresden University of Technology (Author)
  • Masin Abo-Rady - , TUD Dresden University of Technology (Author)
  • Antje Janosh - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Rajat Bhatnagar - , Verge Genomics (Author)
  • Marc Bickle - , Max Planck Institute of Molecular Cell Biology and Genetics (Author)
  • Andrew J. Mouland - , McGill University (Author)
  • Jared Sterneckert - , iPS Cells and Neurodegenerative Disease (Junior Research Group) (Author)


Amyotrophic lateral sclerosis (ALS) arises from an interplay of genetic mutations and environmental factors. ssRNA viruses are possible ALS risk factors, but testing their interaction with mutations such as in FUS, which encodes an RNA-binding protein, has been difficult due to the lack of a human disease model. Here, we use isogenic induced pluripotent stem cell (iPSC)-derived spinal neurons (SNs) to investigate the interaction between ssRNA viruses and mutant FUS. We find that rabies virus (RABV) spreads ALS phenotypes, including the formation of stress granules (SGs) with aberrant composition due to increased levels of FUS protein, as well as neurodegeneration and reduced restriction activity by FUS mutations. Consistent with this, iPSC-derived SNs harboring mutant FUS are more sensitive to human immunodeficiency virus (HIV-1) and Zika viruses (ZIKV). We demonstrate that RABV and HIV-1 exacerbate cytoplasmic mislocalization of FUS. Our results demonstrate that viral infections worsen ALS pathology in SNs with genetic risk factors, suggesting a novel role for viruses in modulating patient phenotypes.


Original languageEnglish
Article number480
JournalFrontiers in cellular neuroscience
Publication statusPublished - 22 Oct 2019

External IDs

ORCID /0000-0002-7688-3124/work/142250021


Sustainable Development Goals

ASJC Scopus subject areas


  • amyotrophic lateral sclerosis, FUS, HIV-1, induced pluripotent stem cells, rabies virus, Zika virus