ATM kinase is activated by sindbis viral vector infection

作者：Pampeno Christine; Hurtado Alicia; Meruelo Daniel^*

来源：Virus Research, 2012, 166(1-2): 97-102.

DOI：10.1016/j.virusres.2012.03.008

• Sindbis
• Alphavirus
• ATM
• Gene therapy vector

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 gamma H2AX 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.

• 出版日期2012-6