Analysis of ALS-related proteins during herpes simplex virus-2 latent infection
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(2020) 17:371
RESEARCH
Open Access
Analysis of ALS-related proteins during herpes simplex virus-2 latent infection Jorge Rubén Cabrera1,2,3†, Ignacio Rodríguez-Izquierdo1,2,3†, José Luis Jiménez2,3,4,5* and María Ángeles Muñoz-Fernández1,2,4,5*
Abstract Background: Genetics 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. Methods: We 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. Results: In 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. Conclusions: Latent 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. Keywords: Herpes simplex virus, Latency, Spinal cord, Neurodegeneration, ALS, Microglia, C9ORF72
Background Neurodegenerative diseases (NDDs) are devastating conditions caused by a degeneration and death of neurons, affecting cognition, behavior, and motor functions. In a limited number of cases, the unique cause of the NDD is a genetic alteration, however, the majority of NDDs * Correspondence: [email protected]; [email protected] † Jorge Rubén Cabrera and Ignacio Rodríguez-Izquierdo contributed equally to this work. 2 Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, España 1 Sección Inmunología, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain Full list of author information is available at the end of the article
cases are idiopathic [1, 2]. This suggests that environmental factors may play an important role in NDDs, either being a direct cause of neurodegeneration or being risk factors for neurodegenera
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