title: ATM kinase is activated by sindbis viral vector infection.
abstract: Sindbis virus is a prototypic member of the Alphavirus genus, Togaviridae family. Sindbis replication results in cellular cytotoxicity, a feature that has been exploited by our laboratory for treatment of in vivo tumors. Understanding the interactions between Sindbis vectors and the host cell can lead to better virus production and increased efficacy of gene therapy vectors. Here we present studies investigating a possible cellular response to genotoxic effects of Sindbis vector infection. The Ataxia Telangiectasia Mutated (ATM) kinase, a sentinel against genomic and cellular stress, was activated by Sindbis vector infection at 3h post infection. ATM substrates, Mcm3 and the γH2AX histone, were subsequently phosphorylated, however, substrates involved with checkpoint arrest of DNA replication, p53, Chk1 and Chk2, were not differentially phosphorylated compared with uninfected cells. The ATM response suggests nuclear pertubation, resulting from cessation of host protein synthesis, as an early event in Sindbis vector infection.
authors.affiliation: Gene Therapy Center, Cancer Institute and Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, United States.
authors.forename: Christine
authors.initials: C
authors.lastname: Pampeno
authors.forename: Alicia
authors.initials: A
authors.lastname: Hurtado
authors.forename: Daniel
authors.initials: D
authors.lastname: Meruelo
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D054884:Host-Pathogen Interactions; D051379:Mice; D064126:Minichromosome Maintenance Complex Component 3; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012845:Sindbis Virus / Q000472:pathogenicity*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; C066470:MCM3 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D064126:Minichromosome Maintenance Complex Component 3