Open AccessPI3K Signaling Regulates Rapamycin-Insensitive Translation Initiation Complex Formation in Vaccinia Virus-Infected Cells
Author(s) -
Izabela Zaborowska,
Derek Walsh
Publication year - 2009
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02284-08
Subject(s) - biology , pi3k/akt/mtor pathway , vaccinia , translation (biology) , tor signaling , repressor , eif4e , microbiology and biotechnology , protein biosynthesis , eukaryotic translation , translational regulation , kinase , virus , signal transduction , virology , messenger rna , gene expression , genetics , gene , recombinant dna
How vaccinia virus (VV) regulates assembly of the host translation initiation complex eIF4F remains unclear. Here, we show that VV activated host PI3K to stimulate downstream mammalian target of rapamycin (mTOR), a kinase that inactivates the translational repressor 4E-BP1. However, although the mTOR inhibitor rapamycin suppressed VV-induced inactivation of 4E-BP1, it failed to inhibit eIF4F assembly. In contrast, PI3K inhibition in VV-infected cells increased the abundance of hypophosphorylated 4E-BP1 and disrupted eIF4F complex formation. PI3K signaling, therefore, plays a critical role in regulating protein production during VV infection, at least in part by controlling the abundance and activity of 4E-BP1.