Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression
<p>Abstract</p> <p>Background</p> <p>In HIV-infected T lymphocytes, NF-κB/Rel transcription factors are major elements involved in the activation of LTR-dependent transcription from latency. Most NF-κB heterodimer p65/p50 is sequestered as an inactive form in the cytopl...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-08-01
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| Series: | Retrovirology |
| Online Access: | http://www.retrovirology.com/content/4/1/56 |
| _version_ | 1828412381964795904 |
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| author | Mittelbrunn Maria Rullas Joaquín López-Huertas María Coiras Mayte Alcamí José |
| author_facet | Mittelbrunn Maria Rullas Joaquín López-Huertas María Coiras Mayte Alcamí José |
| author_sort | Mittelbrunn Maria |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>In HIV-infected T lymphocytes, NF-κB/Rel transcription factors are major elements involved in the activation of LTR-dependent transcription from latency. Most NF-κB heterodimer p65/p50 is sequestered as an inactive form in the cytoplasm of resting T lymphocytes via its interaction with IκB inhibitors. In these cells, both absolute HIV latency and low level ongoing HIV replication have been described. These situations could be related to differences in the balance between NF-κB and IκBα ratio. Actually, control of IκBα by cellular factors such as Murr-1 plays a critical role in maintaining HIV latency in unstimulated T lymphocytes. Formerly, our group demonstrated the presence of nuclear IκBα in T cells after PMA activation. Now we attempt to determine the dynamics of NF-κB/IκBα nucleocytosolic transport in absence of activation as a mechanism to explain both the maintenance of latency and the existence of low level ongoing HIV replication in resting CD<sub>4</sub><sup>+ </sup>T lymphocytes.</p> <p>Results and conclusion</p> <p>We show that the inhibition of the nuclear export by leptomycin B in resting CD<sub>4</sub><sup>+ </sup>T cells resulted in nuclear accumulation of both IκBα and p65/RelA, as well as formation of NF-κB/IκBα complexes. This proves the existence of a rapid shuttling of IκBα between nucleus and cytosol even in absence of cellular activation. The nuclear accumulation of IκBα in resting CD<sub>4</sub><sup>+ </sup>T lymphocytes results in inhibition of HIV-LTR dependent transcription as well as restrains HIV replication in CD<sub>4</sub><sup>+ </sup>T lymphocytes. On the other hand, basal NF-κB activity detected in resting CD<sub>4</sub><sup>+ </sup>T lymphocytes was related to low level HIV replication in these cells.</p> |
| first_indexed | 2024-12-10T12:48:10Z |
| format | Article |
| id | doaj.art-9d357cf0623a44da98dffe496a0b8316 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-12-10T12:48:10Z |
| publishDate | 2007-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-9d357cf0623a44da98dffe496a0b83162022-12-22T01:48:21ZengBMCRetrovirology1742-46902007-08-01415610.1186/1742-4690-4-56Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expressionMittelbrunn MariaRullas JoaquínLópez-Huertas MaríaCoiras MayteAlcamí José<p>Abstract</p> <p>Background</p> <p>In HIV-infected T lymphocytes, NF-κB/Rel transcription factors are major elements involved in the activation of LTR-dependent transcription from latency. Most NF-κB heterodimer p65/p50 is sequestered as an inactive form in the cytoplasm of resting T lymphocytes via its interaction with IκB inhibitors. In these cells, both absolute HIV latency and low level ongoing HIV replication have been described. These situations could be related to differences in the balance between NF-κB and IκBα ratio. Actually, control of IκBα by cellular factors such as Murr-1 plays a critical role in maintaining HIV latency in unstimulated T lymphocytes. Formerly, our group demonstrated the presence of nuclear IκBα in T cells after PMA activation. Now we attempt to determine the dynamics of NF-κB/IκBα nucleocytosolic transport in absence of activation as a mechanism to explain both the maintenance of latency and the existence of low level ongoing HIV replication in resting CD<sub>4</sub><sup>+ </sup>T lymphocytes.</p> <p>Results and conclusion</p> <p>We show that the inhibition of the nuclear export by leptomycin B in resting CD<sub>4</sub><sup>+ </sup>T cells resulted in nuclear accumulation of both IκBα and p65/RelA, as well as formation of NF-κB/IκBα complexes. This proves the existence of a rapid shuttling of IκBα between nucleus and cytosol even in absence of cellular activation. The nuclear accumulation of IκBα in resting CD<sub>4</sub><sup>+ </sup>T lymphocytes results in inhibition of HIV-LTR dependent transcription as well as restrains HIV replication in CD<sub>4</sub><sup>+ </sup>T lymphocytes. On the other hand, basal NF-κB activity detected in resting CD<sub>4</sub><sup>+ </sup>T lymphocytes was related to low level HIV replication in these cells.</p>http://www.retrovirology.com/content/4/1/56 |
| spellingShingle | Mittelbrunn Maria Rullas Joaquín López-Huertas María Coiras Mayte Alcamí José Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression Retrovirology |
| title | Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression |
| title_full | Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression |
| title_fullStr | Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression |
| title_full_unstemmed | Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression |
| title_short | Basal shuttle of NF-κB/IκBα in resting T lymphocytes regulates HIV-1 LTR dependent expression |
| title_sort | basal shuttle of nf κb iκbα in resting t lymphocytes regulates hiv 1 ltr dependent expression |
| url | http://www.retrovirology.com/content/4/1/56 |
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