Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub>
<p>Abstract</p> <p>Background</p> <p>The 5' untranslated region (UTR) or leader sequence of simian immunodeficiency virus (SIV<sub>mac239</sub>) is multifunctional and harbors the regulatory elements for viral replication, persistence, gene translation,...
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| Format: | Article |
| Language: | English |
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BMC
2006-12-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/3/1/96 |
| _version_ | 1819140192825507840 |
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| author | Whitney James B Wainberg Mark A |
| author_facet | Whitney James B Wainberg Mark A |
| author_sort | Whitney James B |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The 5' untranslated region (UTR) or leader sequence of simian immunodeficiency virus (SIV<sub>mac239</sub>) is multifunctional and harbors the regulatory elements for viral replication, persistence, gene translation, expression, and the packaging and dimerization of viral genomic RNA (vRNA). We have constructed a series of deletions in the SIV<sub>mac239 </sub>leader sequence in order to determine the involvement of this region in both the packaging and dimerization of viral genomic RNA. We also assessed the impact of these deletions upon viral infectiousness, replication kinetics and gene expression in cell lines and monkey peripheral blood mononuclear cells (PBMC).</p> <p>Results</p> <p>Regions on both sides of the major splice donor (SD) were found to be necessary for the efficiency and specificity of viral genome packaging. However, stem-loop1 is critical for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the initiation site of SIV-Gag have additive effects on RNA packaging and contribute to a lesser degree to RNA dimerization. The targeted disruption of structures on both sides of the SD also severely impacts viral infectiousness, gene expression and replication in both CEMx174 cells and rhesus PBMC.</p> <p>Conclusion</p> <p>In the leader region of SIV<sub>mac239</sub>, stem-loop1 functions as the primary determinant for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the translational initiation site of SIV-Gag are classified as secondary determinants and play a role in dimerization. Collectively, these data signify a linkage between the primary encapsidation determinant of SIV<sub>mac239 </sub>and RNA dimerization.</p> |
| first_indexed | 2024-12-22T11:34:39Z |
| format | Article |
| id | doaj.art-5976bd11de0e482ab4264f6b9fb91540 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-22T11:34:39Z |
| publishDate | 2006-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-5976bd11de0e482ab4264f6b9fb915402022-12-21T18:27:28ZengBMCRetrovirology1742-46902006-12-01319610.1186/1742-4690-3-96Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub>Whitney James BWainberg Mark A<p>Abstract</p> <p>Background</p> <p>The 5' untranslated region (UTR) or leader sequence of simian immunodeficiency virus (SIV<sub>mac239</sub>) is multifunctional and harbors the regulatory elements for viral replication, persistence, gene translation, expression, and the packaging and dimerization of viral genomic RNA (vRNA). We have constructed a series of deletions in the SIV<sub>mac239 </sub>leader sequence in order to determine the involvement of this region in both the packaging and dimerization of viral genomic RNA. We also assessed the impact of these deletions upon viral infectiousness, replication kinetics and gene expression in cell lines and monkey peripheral blood mononuclear cells (PBMC).</p> <p>Results</p> <p>Regions on both sides of the major splice donor (SD) were found to be necessary for the efficiency and specificity of viral genome packaging. However, stem-loop1 is critical for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the initiation site of SIV-Gag have additive effects on RNA packaging and contribute to a lesser degree to RNA dimerization. The targeted disruption of structures on both sides of the SD also severely impacts viral infectiousness, gene expression and replication in both CEMx174 cells and rhesus PBMC.</p> <p>Conclusion</p> <p>In the leader region of SIV<sub>mac239</sub>, stem-loop1 functions as the primary determinant for both RNA encapsidation and dimerization. Downstream elements between the splice donor and the translational initiation site of SIV-Gag are classified as secondary determinants and play a role in dimerization. Collectively, these data signify a linkage between the primary encapsidation determinant of SIV<sub>mac239 </sub>and RNA dimerization.</p>http://www.retrovirology.com/content/3/1/96 |
| spellingShingle | Whitney James B Wainberg Mark A Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub> Retrovirology |
| title | Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub> |
| title_full | Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub> |
| title_fullStr | Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub> |
| title_full_unstemmed | Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub> |
| title_short | Impaired RNA incorporation and dimerization in live attenuated leader-variants of SIV<sub>mac239</sub> |
| title_sort | impaired rna incorporation and dimerization in live attenuated leader variants of siv sub mac239 sub |
| url | http://www.retrovirology.com/content/3/1/96 |
| work_keys_str_mv | AT whitneyjamesb impairedrnaincorporationanddimerizationinliveattenuatedleadervariantsofsivsubmac239sub AT wainbergmarka impairedrnaincorporationanddimerizationinliveattenuatedleadervariantsofsivsubmac239sub |