RGD Reference Report - Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection. - Rat Genome Database

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

Authors: Sheng, J  Organ, EL  Hao, C  Wells, KS  Ruley, HE  Rubin, DH 
Citation: Sheng J, etal., BMC Cell Biol. 2004 Aug 27;5:32.
RGD ID: 2311622
Pubmed: PMID:15333144   (View Abstract at PubMed)
PMCID: PMC517494   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2121-5-32   (Journal Full-text)

BACKGROUND: 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. RESULTS: 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 proliferate in soft agar, a phenotype associated with malignant growth in vivo. CONCLUSION: These results indicate that IGF-II, and by inference other components of the IGF-II signalling pathway, can confer resistance to lytic reovirus infection. This report represents the first use of gene entrapment to identify host factors affecting virus infection. Concomitant transformation observed in some virus resistant cells illustrates a potential mechanism of carcinogenesis associated with chronic virus infection.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Reoviridae Infections resistanceISOIgf2r (Rattus norvegicus)2311622; 2311622 RGD 
Reoviridae Infections resistanceIAGP 2311622 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of defense response to virus  IMP 2311622 RGD 
positive regulation of epithelial cell proliferation  IMP 2311622in soft agarRGD 

Objects Annotated

Genes (Rattus norvegicus)
Htra1  (HtrA serine peptidase 1)
Igf2r  (insulin-like growth factor 2 receptor)

Genes (Mus musculus)
Igf2r  (insulin-like growth factor 2 receptor)

Genes (Homo sapiens)
IGF2R  (insulin like growth factor 2 receptor)


Additional Information