Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal
<p>Abstract</p> <p>Background</p> <p>The integrase (IN) of human immunodeficiency virus type 1 (HIV-1) has been implicated in different steps during viral replication, including nuclear import of the viral pre-integration complex. The exact mechanisms underlying the nuc...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-12-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/6/1/112 |
| _version_ | 1818808365407535104 |
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| author | Waigmann Elisabeth Graessmann Adolf Melamed-Book Naomi Rosenbluh Joseph Armon-Omer Ayelet Levin Aviad Loyter Abraham |
| author_facet | Waigmann Elisabeth Graessmann Adolf Melamed-Book Naomi Rosenbluh Joseph Armon-Omer Ayelet Levin Aviad Loyter Abraham |
| author_sort | Waigmann Elisabeth |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The integrase (IN) of human immunodeficiency virus type 1 (HIV-1) has been implicated in different steps during viral replication, including nuclear import of the viral pre-integration complex. The exact mechanisms underlying the nuclear import of IN and especially the question of whether it bears a functional nuclear localization signal (NLS) remain controversial.</p> <p>Results</p> <p>Here, we studied the nuclear import pathway of IN by using multiple <it>in vivo </it>and <it>in vitro </it>systems. Nuclear import was not observed in an importin α temperature-sensitive yeast mutant, indicating an importin α-mediated process. Direct interaction between the full-length IN and importin α was demonstrated <it>in vivo </it>using bimolecular fluorescence complementation assay (BiFC). Nuclear import studies in yeast cells, with permeabilized mammalian cells, or microinjected cultured mammalian cells strongly suggest that the IN bears a NLS domain located between residues 161 and 173. A peptide bearing this sequence -NLS-IN peptide- inhibited nuclear accumulation of IN in transfected cell-cycle arrested cells. Integration of viral cDNA as well as HIV-1 replication in viral cell-cycle arrested infected cells were blocked by the NLS-IN peptide.</p> <p>Conclusion</p> <p>Our present findings support the view that nuclear import of IN occurs via the importin α pathway and is promoted by a specific NLS domain. This import could be blocked by NLS-IN peptide, resulting in inhibition of viral infection, confirming the view that nuclear import of the viral pre-integration complex is mediated by viral IN.</p> |
| first_indexed | 2024-12-18T19:40:24Z |
| format | Article |
| id | doaj.art-4c5e1eb500ac416f90e7d2c367b64d39 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-18T19:40:24Z |
| publishDate | 2009-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-4c5e1eb500ac416f90e7d2c367b64d392022-12-21T20:55:27ZengBMCRetrovirology1742-46902009-12-016111210.1186/1742-4690-6-112Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signalWaigmann ElisabethGraessmann AdolfMelamed-Book NaomiRosenbluh JosephArmon-Omer AyeletLevin AviadLoyter Abraham<p>Abstract</p> <p>Background</p> <p>The integrase (IN) of human immunodeficiency virus type 1 (HIV-1) has been implicated in different steps during viral replication, including nuclear import of the viral pre-integration complex. The exact mechanisms underlying the nuclear import of IN and especially the question of whether it bears a functional nuclear localization signal (NLS) remain controversial.</p> <p>Results</p> <p>Here, we studied the nuclear import pathway of IN by using multiple <it>in vivo </it>and <it>in vitro </it>systems. Nuclear import was not observed in an importin α temperature-sensitive yeast mutant, indicating an importin α-mediated process. Direct interaction between the full-length IN and importin α was demonstrated <it>in vivo </it>using bimolecular fluorescence complementation assay (BiFC). Nuclear import studies in yeast cells, with permeabilized mammalian cells, or microinjected cultured mammalian cells strongly suggest that the IN bears a NLS domain located between residues 161 and 173. A peptide bearing this sequence -NLS-IN peptide- inhibited nuclear accumulation of IN in transfected cell-cycle arrested cells. Integration of viral cDNA as well as HIV-1 replication in viral cell-cycle arrested infected cells were blocked by the NLS-IN peptide.</p> <p>Conclusion</p> <p>Our present findings support the view that nuclear import of IN occurs via the importin α pathway and is promoted by a specific NLS domain. This import could be blocked by NLS-IN peptide, resulting in inhibition of viral infection, confirming the view that nuclear import of the viral pre-integration complex is mediated by viral IN.</p>http://www.retrovirology.com/content/6/1/112 |
| spellingShingle | Waigmann Elisabeth Graessmann Adolf Melamed-Book Naomi Rosenbluh Joseph Armon-Omer Ayelet Levin Aviad Loyter Abraham Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal Retrovirology |
| title | Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal |
| title_full | Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal |
| title_fullStr | Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal |
| title_full_unstemmed | Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal |
| title_short | Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal |
| title_sort | inhibition of hiv 1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal |
| url | http://www.retrovirology.com/content/6/1/112 |
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