Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line
Avian leukosis virus (ALV) induces B-cell lymphomas and other malignancies in chickens through insertional activation of oncogenes, and <i>c-myc</i> activation has been commonly identified in ALV-induced tumors. Using ALV-transformed B-lymphoma-derived HP45 cell line, we applied in situ...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11263 |
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| author | Swagata Roy Megha Sravani Bondada Yaoyao Zhang Katy Moffat Venugopal Nair Yongxiu Yao |
| author_facet | Swagata Roy Megha Sravani Bondada Yaoyao Zhang Katy Moffat Venugopal Nair Yongxiu Yao |
| author_sort | Swagata Roy |
| collection | DOAJ |
| description | Avian leukosis virus (ALV) induces B-cell lymphomas and other malignancies in chickens through insertional activation of oncogenes, and <i>c-myc</i> activation has been commonly identified in ALV-induced tumors. Using ALV-transformed B-lymphoma-derived HP45 cell line, we applied in situ CRISPR-Cas9 editing of integrated proviral long terminal repeat (LTR) to examine the effects on gene expression and cell proliferation. Targeted deletion of LTR resulted in significant reduction in expression of a number of LTR-regulated genes including <i>c-myc</i>. LTR deletion also induced apoptosis of HP45 cells, affecting their proliferation, demonstrating the significance of LTR-mediated regulation of critical genes. Compared to the global effects on expression and functions of multiple genes in LTR-deleted cells, deletion of <i>c-myc</i> had a major effect on the HP45 cells proliferation with the phenotype similar to the LTR deletion, demonstrating the significance of <i>c-myc</i> expression in ALV-induced lymphomagenesis. Overall, our studies have not only shown the potential of targeted editing of the LTR for the global inhibition of retrovirus-induced transformation, but also have provided insights into the roles of LTR-regulated genes in ALV-induced neoplastic transformation. |
| first_indexed | 2024-03-09T21:41:21Z |
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| id | doaj.art-d11799d8ebe14117a0d200498626c345 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:41:21Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d11799d8ebe14117a0d200498626c3452023-11-23T20:30:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191126310.3390/ijms231911263Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell LineSwagata Roy0Megha Sravani Bondada1Yaoyao Zhang2Katy Moffat3Venugopal Nair4Yongxiu Yao5The Pirbright Institute, Pirbright, Woking GU24 0NF, UKThe Pirbright Institute, Pirbright, Woking GU24 0NF, UKThe Pirbright Institute, Pirbright, Woking GU24 0NF, UKThe Pirbright Institute, Pirbright, Woking GU24 0NF, UKThe Pirbright Institute, Pirbright, Woking GU24 0NF, UKThe Pirbright Institute, Pirbright, Woking GU24 0NF, UKAvian leukosis virus (ALV) induces B-cell lymphomas and other malignancies in chickens through insertional activation of oncogenes, and <i>c-myc</i> activation has been commonly identified in ALV-induced tumors. Using ALV-transformed B-lymphoma-derived HP45 cell line, we applied in situ CRISPR-Cas9 editing of integrated proviral long terminal repeat (LTR) to examine the effects on gene expression and cell proliferation. Targeted deletion of LTR resulted in significant reduction in expression of a number of LTR-regulated genes including <i>c-myc</i>. LTR deletion also induced apoptosis of HP45 cells, affecting their proliferation, demonstrating the significance of LTR-mediated regulation of critical genes. Compared to the global effects on expression and functions of multiple genes in LTR-deleted cells, deletion of <i>c-myc</i> had a major effect on the HP45 cells proliferation with the phenotype similar to the LTR deletion, demonstrating the significance of <i>c-myc</i> expression in ALV-induced lymphomagenesis. Overall, our studies have not only shown the potential of targeted editing of the LTR for the global inhibition of retrovirus-induced transformation, but also have provided insights into the roles of LTR-regulated genes in ALV-induced neoplastic transformation.https://www.mdpi.com/1422-0067/23/19/11263avian leukosis virusintegrationLTR<i>c-myc</i> |
| spellingShingle | Swagata Roy Megha Sravani Bondada Yaoyao Zhang Katy Moffat Venugopal Nair Yongxiu Yao Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line International Journal of Molecular Sciences avian leukosis virus integration LTR <i>c-myc</i> |
| title | Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line |
| title_full | Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line |
| title_fullStr | Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line |
| title_full_unstemmed | Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line |
| title_short | Proviral ALV-LTR Sequence Is Essential for Continued Proliferation of the ALV-Transformed B Cell Line |
| title_sort | proviral alv ltr sequence is essential for continued proliferation of the alv transformed b cell line |
| topic | avian leukosis virus integration LTR <i>c-myc</i> |
| url | https://www.mdpi.com/1422-0067/23/19/11263 |
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