Echovirus 30 induced neuronal cell death through TRIO-RhoA signaling activation

• Published in: PloS one 2012-05, Vol.7 (5), p.e36656-e36656
• Main Authors: Lee, June-Woo, Yeo, Sang-Gu, Kang, Byung-Hak, Lee, Hoe-Kyu, Kim, Jin-Won, Lee, Sun-Hwa, Kim, Ki-Sang, Cheon, Doo-Sung
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Aseptic meningitis; Axon guidance; Biochemistry; Biology; Cell activation; Cell adhesion & migration; Cell cycle; Cell death; Cell Death - genetics; Cell Line, Tumor; Cell migration; Dietary fiber; Echovirus; Echovirus Infections - genetics; Echovirus Infections - metabolism; Encephalitis; Enterovirus; Enterovirus B, Human - genetics; Enterovirus B, Human - metabolism; Epidemics; Fibroblasts; Gel electrophoresis; Gene Expression Profiling; Gene Expression Regulation; Guanine; Guanine nucleotide exchange factor; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; Health aspects; Hepatitis; Humans; Identification; Infections; Infectious diseases; Investigations; Kinases; Leukocyte migration; Medicine; Meningitis; Mortality; Nervous system; Neuroblastoma; Neurons; Neurons - metabolism; Nitric oxide; Nitric Oxide - metabolism; Pathogenesis; Protein expression; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; rhoA GTP-Binding Protein - antagonists & inhibitors; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; RhoA protein; Signal Transduction; Signaling; Spectrophotometry; Transcriptional Activation; Two dimensional analysis; Viral infections; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036656

Echovirus 30 (Echo30) is one of the most frequently identified human enteroviruses (EVs) causing aseptic meningitis and encephalitis. However the mechanism underlying the pathogenesis of Echo30 infection with significant clinical outcomes is not completely understood. The aim of this investigation is to illustrate molecular pathologic alteration in neuronal cells induced by Echo30 infection using clinical isolate from young patient with neurologic involvement. To characterize the neuronal cellular response to Echo30 infection, we performed a proteomic analysis based on two-dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF Mass Spectrophotometric (MS) analysis. We identified significant alteration of several protein expression levels in Echo30-infected SK-N-SH cells. Among these proteins, we focused on an outstanding up-regulation of Triple functional domain (TRIO) in Echo30-infected SK-N-SH cells. Generally, TRIO acts as a key component in the regulation of axon guidance and cell migration. In this study, we determined that TRIO plays a role in the novel pathways in Echo30 induced neuronal cell death. Our finding shows that TRIO plays a critical role in neuronal cell death by Echo30 infection. Echo30 infection activates TRIO-guanine nucleotide exchange factor (GEF) domains (GEFD2) and RhoA signaling in turn. These results suggest that Echo30 infection induced neuronal cell death by activation of the TRIO-RhoA signaling. We expect the regulation of TRIO-RhoA signaling may represent a new therapeutic approach in treating aseptic meningitis and encephalitis induced by Echo30.