Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells
<p>Abstract</p> <p>Background</p> <p>All human immunodeficiency virus (HIV-1) uses a host tRNA<sup>Lys,3 </sup>as the primer for reverse transcription. The tRNA<sup>Lys,3 </sup>is bound to a region on the HIV-1 genome, the primer-binding site (PB...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2005-03-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/2/1/21 |
| _version_ | 1818497246748999680 |
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| author | Kirkman Richard L Kosloff Barry R Moore-Rigdon Kenda L Morrow Casey D |
| author_facet | Kirkman Richard L Kosloff Barry R Moore-Rigdon Kenda L Morrow Casey D |
| author_sort | Kirkman Richard L |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>All human immunodeficiency virus (HIV-1) uses a host tRNA<sup>Lys,3 </sup>as the primer for reverse transcription. The tRNA<sup>Lys,3 </sup>is bound to a region on the HIV-1 genome, the primer-binding site (PBS), that is complementary to the 18 terminal nucleotides of tRNA<sup>Lys,3</sup>. How HIV-1 selects the tRNA from the intracellular milieu is unresolved.</p> <p>Results</p> <p>HIV-1 tRNA primer selection has been investigated using viruses in which the primer-binding site (PBS) and a sequence within U5 were altered so as to be complementary to tRNA<sup>Met</sup>, tRNA<sup>Pro </sup>or tRNA<sup>Ile</sup>. Analysis of the replication of these viruses in human peripheral blood mononuclear cells (PBMC) revealed preferences for the selection of certain tRNAs. HIV-1 with the PBS altered to be complementary to tRNA<sup>Met</sup>, with and without the additional mutation in U5 to be complementary to the anticodon of tRNA<sup>Met</sup>, stably maintains the PBS complementary to tRNA<sup>Met </sup>following extended <it>in vitro </it>culture in PBMC. In contrast, viruses with either the PBS or PBS and U5 mutated to be complementary to tRNA<sup>Ile </sup>were unstable during <it>in vitro </it>replication in PBMC and reverted to utilize tRNA<sup>Lys,3</sup>. Viruses with the PBS altered to be complementary to tRNA<sup>Pro </sup>replicated in PBMC but reverted to use tRNA<sup>Lys,3</sup>; viruses with mutations in both the U5 and PBS complementary to tRNA<sup>Pro </sup>maintained this PBS, yet replicated poorly in PBMC.</p> <p>Conclusion</p> <p>The results of these studies demonstrate that HIV-1 has preferences for selection of certain tRNAs for high-level replication in PBMC.</p> |
| first_indexed | 2024-12-10T18:43:17Z |
| format | Article |
| id | doaj.art-ce22828a7759494d97b809f961cb09f3 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-10T18:43:17Z |
| publishDate | 2005-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-ce22828a7759494d97b809f961cb09f32022-12-22T01:37:36ZengBMCRetrovirology1742-46902005-03-01212110.1186/1742-4690-2-21Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cellsKirkman Richard LKosloff Barry RMoore-Rigdon Kenda LMorrow Casey D<p>Abstract</p> <p>Background</p> <p>All human immunodeficiency virus (HIV-1) uses a host tRNA<sup>Lys,3 </sup>as the primer for reverse transcription. The tRNA<sup>Lys,3 </sup>is bound to a region on the HIV-1 genome, the primer-binding site (PBS), that is complementary to the 18 terminal nucleotides of tRNA<sup>Lys,3</sup>. How HIV-1 selects the tRNA from the intracellular milieu is unresolved.</p> <p>Results</p> <p>HIV-1 tRNA primer selection has been investigated using viruses in which the primer-binding site (PBS) and a sequence within U5 were altered so as to be complementary to tRNA<sup>Met</sup>, tRNA<sup>Pro </sup>or tRNA<sup>Ile</sup>. Analysis of the replication of these viruses in human peripheral blood mononuclear cells (PBMC) revealed preferences for the selection of certain tRNAs. HIV-1 with the PBS altered to be complementary to tRNA<sup>Met</sup>, with and without the additional mutation in U5 to be complementary to the anticodon of tRNA<sup>Met</sup>, stably maintains the PBS complementary to tRNA<sup>Met </sup>following extended <it>in vitro </it>culture in PBMC. In contrast, viruses with either the PBS or PBS and U5 mutated to be complementary to tRNA<sup>Ile </sup>were unstable during <it>in vitro </it>replication in PBMC and reverted to utilize tRNA<sup>Lys,3</sup>. Viruses with the PBS altered to be complementary to tRNA<sup>Pro </sup>replicated in PBMC but reverted to use tRNA<sup>Lys,3</sup>; viruses with mutations in both the U5 and PBS complementary to tRNA<sup>Pro </sup>maintained this PBS, yet replicated poorly in PBMC.</p> <p>Conclusion</p> <p>The results of these studies demonstrate that HIV-1 has preferences for selection of certain tRNAs for high-level replication in PBMC.</p>http://www.retrovirology.com/content/2/1/21 |
| spellingShingle | Kirkman Richard L Kosloff Barry R Moore-Rigdon Kenda L Morrow Casey D Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells Retrovirology |
| title | Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells |
| title_full | Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells |
| title_fullStr | Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells |
| title_full_unstemmed | Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells |
| title_short | Preferences for the selection of unique tRNA primers revealed from analysis of HIV-1 replication in peripheral blood mononuclear cells |
| title_sort | preferences for the selection of unique trna primers revealed from analysis of hiv 1 replication in peripheral blood mononuclear cells |
| url | http://www.retrovirology.com/content/2/1/21 |
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