Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection

BMC Cell Biology
Jinsong ShengD H Rubin

Abstract

Viruses are obligate intracellular parasites and rely upon the host cell for different steps in their life cycles. The characterization of cellular genes required for virus infection and/or cell killing will be essential for understanding viral life cycles, and may provide cellular targets for new antiviral therapies. A gene entrapment approach was used to identify candidate cellular genes that affect reovirus infection or virus induced cell lysis. Four of the 111 genes disrupted in clones selected for resistance to infection by reovirus type 1 involved the insulin growth factor-2 (IGF-II) pathway, including: the mannose-6-phosphate/IGF2 receptor (Igf2r), a protease associated with insulin growth factor binding protein 5 (Prss11), and the CTCF transcriptional regulator (Ctcf). The disruption of Ctcf, which encodes a repressor of Igf2, was associated with enhanced Igf2 gene expression. Plasmids expressing either the IGF-II pro-hormone or IGF-II without the carboxy terminal extension (E)-peptide sequence independently conferred high levels of cellular resistance to reovirus infection. Forced IGF-II expression results in a block in virus disassembly. In addition, Ctcf disruption and forced Igf2 expression both enabled cells to pro...Continue Reading

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Citations

Mar 13, 2012·AIDS Research and Human Retroviruses·Natallia DziubaJames L Murray
Oct 26, 2006·Nucleic Acids Research·Qing LinH Earl Ruley
Nov 4, 2004·BMC Cell Biology·Edward L OrganDonald H Rubin
May 17, 2011·Retrovirology·Brian M FriedrichMonique R Ferguson
Jan 31, 2014·Molecular Biotechnology·James L MurrayDonald H Rubin
Nov 18, 2009·Expert Opinion on Biological Therapy·Diana J M Van Den WollenbergRob C Hoeben
Nov 6, 2013·Infection and Immunity·Jana N RadinTimothy L Cover

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Datasets Mentioned

BETA
X17012

Methods Mentioned

BETA
gene trap
PCR
protein assay
Assay

Software Mentioned

BLAST

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