Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection
<p>Abstract</p> <p>Background</p> <p>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 understa...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2004-08-01
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| Series: | BMC Cell Biology |
| Online Access: | http://www.biomedcentral.com/1471-2121/5/32 |
| _version_ | 1818790951263404032 |
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| author | Hao Chuanming Organ Edward L Sheng Jinsong Wells K Sam Ruley H Earl Rubin Donald H |
| author_facet | Hao Chuanming Organ Edward L Sheng Jinsong Wells K Sam Ruley H Earl Rubin Donald H |
| author_sort | Hao Chuanming |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 (<it>Igf2r</it>), a protease associated with insulin growth factor binding protein 5 (<it>Prss11</it>), and the CTCF transcriptional regulator (<it>Ctcf</it>). The disruption of <it>Ctcf</it>, which encodes a repressor of <it>Igf2</it>, was associated with enhanced <it>Igf2 </it>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, <it>Ctcf </it>disruption and forced <it>Igf2 </it>expression both enabled cells to proliferate in soft agar, a phenotype associated with malignant growth <it>in vivo</it>.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-18T15:03:37Z |
| format | Article |
| id | doaj.art-a94702044b4d458082b9342f012f899a |
| institution | Directory Open Access Journal |
| issn | 1471-2121 |
| language | English |
| last_indexed | 2024-12-18T15:03:37Z |
| publishDate | 2004-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cell Biology |
| spelling | doaj.art-a94702044b4d458082b9342f012f899a2022-12-21T21:03:50ZengBMCBMC Cell Biology1471-21212004-08-01513210.1186/1471-2121-5-32Mutations in the IGF-II pathway that confer resistance to lytic reovirus infectionHao ChuanmingOrgan Edward LSheng JinsongWells K SamRuley H EarlRubin Donald H<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 (<it>Igf2r</it>), a protease associated with insulin growth factor binding protein 5 (<it>Prss11</it>), and the CTCF transcriptional regulator (<it>Ctcf</it>). The disruption of <it>Ctcf</it>, which encodes a repressor of <it>Igf2</it>, was associated with enhanced <it>Igf2 </it>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, <it>Ctcf </it>disruption and forced <it>Igf2 </it>expression both enabled cells to proliferate in soft agar, a phenotype associated with malignant growth <it>in vivo</it>.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2121/5/32 |
| spellingShingle | Hao Chuanming Organ Edward L Sheng Jinsong Wells K Sam Ruley H Earl Rubin Donald H Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection BMC Cell Biology |
| title | Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection |
| title_full | Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection |
| title_fullStr | Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection |
| title_full_unstemmed | Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection |
| title_short | Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection |
| title_sort | mutations in the igf ii pathway that confer resistance to lytic reovirus infection |
| url | http://www.biomedcentral.com/1471-2121/5/32 |
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