title: Echovirus 30 induced neuronal cell death through TRIO-RhoA signaling activation.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Enteric and Hepatitis Viruses, Center for Infectious Diseases, National Institutes of Health, Osong, Korea.
authors.forename: June-Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Yeo
authors.forename: Byung-Hak
authors.initials: BH
authors.lastname: Kang
authors.forename: Hoe-Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Ki-Sang
authors.initials: KS
authors.lastname: Kim
authors.forename: Doo-Sung
authors.initials: DS
authors.lastname: Cheon
mesh_terms: D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D004457:Echovirus Infections / Q000235:genetics / Q000378:metabolism; D029822:Enterovirus B, Human / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015533:Transcriptional Activation; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C066737:RHOA protein, human; D009569:Nitric Oxide; D017346:Protein Serine-Threonine Kinases; C099628:TRIO protein, human; D020742:rhoA GTP-Binding Protein