Enteroviral Infection: The Forgotten Link to Amyotrophic Lateral Sclerosis?
FRONTIERS IN MOLECULAR NEUROSCIENCE
Authors: Xue, Yuan Chao; Feuer, Ralph; Cashman, Neil; Luo, Honglin
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily attacks motor neurons in the brain and spinal cord, leading to progressive paralysis and ultimately death. Currently there is no effective therapy. The majority of ALS cases are sporadic, with no known family history; unfortunately the etiology remains largely unknown. Contribution of Enteroviruses (EVs), a family of positive-stranded RNA viruses including poliovirus, coxsackievirus, echovirus, enterovirus-A71 and enterovirus-D68, to the development of ALS has been suspected as they can target motor neurons, and patients with prior poliomyelitis show a higher risk of motor neuron disease. Multiple efforts have been made to detect enteroviral genome in ALS patient tissues over the past two decades; however the clinical data are controversial and a causal relationship has not yet been established. Recent evidence from in vitro and animal studies suggests that enterovirus-induced pathology remarkably resembles the cellular and molecular phenotype of ALS, indicating a possible link between enteroviral infection and ALS pathogenesis. In this review, we summarize the nature of enteroviral infection, including route of infection, cells targeted, and viral persistence within the central nervous system (CNS). We review the molecular mechanisms underlying viral infection and highlight the similarity between viral pathogenesis and the molecular and pathological features of ALS, and finally, discuss the potential role of enteroviral infection in frontotemporal dementia (FTD), a disease that shares common clinical, genetic, and pathological features with ALS, and the significance of anti-viral therapy as an option for the treatment of ALS.
Identification of different respiratory viruses, after a cell culture step, by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)
SCIENTIFIC REPORTS
Authors: Calderaro, Adriana; Arcangeletti, Maria Cristina; Rodighiero, Isabella; Buttrini, Mirko; Montecchini, Sara; Simone, Rosita Vasile; Medici, Maria Cristina; Chezzi, Carlo; De Conto, Flora
Abstract
In this study matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), a reliable identification method for the diagnosis of bacterial and fungal infections, is presented as an innovative tool to investigate the protein profile of cell cultures infected by the most common viruses causing respiratory tract infections in humans. MALDI-TOF MS was applied to the identification of influenza A and B viruses, adenovirus C species, parainfluenza virus types 1, 2 and 3, respiratory syncytial virus, echovirus, cytomegalovirus and metapneumovirus. In this study MALDI-TOF MS was proposed as a model to be applied to the identification of cultivable respiratory viruses using cell culture as a viral proteins enrichment method to the proteome profiling of virus infected and uninfected cell cultures. The reference virus strains and 58 viruses identified from respiratory samples of subjects with respiratory diseases positive for one of the above mentioned viral agents by cell culture were used for the in vitro infection of suitable cell cultures. The isolated viral particles, concentrated by ultracentrifugation, were used for subsequent protein extraction and their spectra profiles were generated by MALDI-TOF MS analysis. The newly created library allowed us to discriminate between uninfected and respiratory virus infected cell cultures.