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

Bellmann, J., Monette, A., Tripathy, V., Sójka, A., Abo-Rady, M., Janosh, A., et al. (2019). Viral Infections Exacerbate FUS-ALS Phenotypes in iPSC-Derived Spinal Neurons in a Virus Species-Specific Manner. Frontiers in cellular neuroscience, 13: 480. doi:10.3389/fncel.2019.00480.

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 Creators:
Bellmann, Jessica, Author
Monette, Anne, Author
Tripathy, Vadreenath, Author
Sójka, Anna, Author
Abo-Rady, Masin, Author
Janosh, Antje, Author
Bhatnagar, Rajat, Author
Bickle, Marc1, Author           
Mouland, Andrew J, Author
Sterneckert, Jared, Author
Affiliations:
1Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: 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.

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 Dates: 2019-01-01
 Publication Status: Issued
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 Identifiers: DOI: 10.3389/fncel.2019.00480
Other: cbg-7552
PMID: 31695598
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Title: Frontiers in cellular neuroscience
  Other : Front Cell Neurosci
Source Genre: Journal
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Pages: - Volume / Issue: 13 Sequence Number: 480 Start / End Page: - Identifier: -