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Analysis of ALS-related proteins during herpes simplex virus-2 latent infection

Authors
  • Cabrera, Jorge Rubén1, 2, 1
  • Rodríguez-Izquierdo, Ignacio1, 2, 1
  • Jiménez, José Luis2, 1, 3, 4
  • Muñoz-Fernández, María Ángeles1, 2, 3, 4
  • 1 Hospital General Universitario Gregorio Marañón, Madrid, Spain , Madrid (Spain)
  • 2 Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España , Madrid (Spain)
  • 3 Spain HIV HGM BioBanco, Madrid, Spain , Madrid (Spain)
  • 4 Biomaterials and Nanomedicine (CIBER-BBN), C/Dr. Esquerdo 46, Madrid, 28007, Spain , Madrid (Spain)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Dec 07, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12974-020-02044-4
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundGenetics have provided hints on potential molecular pathways involved in neurodegenerative diseases (NDD). However, the number of cases caused exclusively by genetic alterations is low, suggesting an important contribution of environmental factors to NDDs. Among these factors, viruses like herpes simplex viruses (HSV-2), capable of establishing lifelong infections within the nervous system (NS), are being proposed to have a role in NDDs. Despite promising data, there is a significant lack of knowledge on this and an urgent need for more research.MethodsWe have set up a mouse model to study HSV latency and its associated neuroinflammation in the spinal cord. The goal of this model was to observe neuroinflammatory changes caused by HSV latent infections, and if those changes were similar to alterations observed in the spinal cord of amyotrophic lateral sclerosis (ALS) patients.ResultsIn infected spinal cords, we have observed a strong leukocyte infiltration and a severe alteration of microglia close to motor neurons. We have also analyzed ALS-related proteins: we have not found changes in TDP-43 and Fus in neurons, but interestingly, we have found decreased protein levels of C9orf72, of which coding gene is severely altered in some familial forms of ALS and is critical for microglia homeostasis.ConclusionsLatent infection of HSV in the spinal cord showed altered microglia and leukocyte infiltration. These inflammatory features resembled to those observed in the spinal cord of ALS patients. No changes mimicking ALS neuropathology, such as TDP-43 cytoplasmic inclusions, were found in infected spinal cords, but a decrease in protein levels of C9orf72 was observed. Then, further studies should be required to determine whether HSV-2 has a role in ALS.

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