The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection.
The causative mutation responsible for limb girdle muscular dystrophy 1F (LGMD1F) is one heterozygous single nucleotide deletion in the stop codon of the nuclear import factor Transportin 3 gene (TNPO3). This mutation causes a carboxy-terminal extension of 15 amino acids, producing a protein of unkn...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1007958 |
| _version_ | 1819260848473899008 |
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| author | Sara Rodríguez-Mora Flore De Wit Javier García-Perez Mercedes Bermejo María Rosa López-Huertas Elena Mateos Pilar Martí Susana Rocha Lorena Vigón Frauke Christ Zeger Debyser Juan Jesús Vílchez Mayte Coiras José Alcamí |
| author_facet | Sara Rodríguez-Mora Flore De Wit Javier García-Perez Mercedes Bermejo María Rosa López-Huertas Elena Mateos Pilar Martí Susana Rocha Lorena Vigón Frauke Christ Zeger Debyser Juan Jesús Vílchez Mayte Coiras José Alcamí |
| author_sort | Sara Rodríguez-Mora |
| collection | DOAJ |
| description | The causative mutation responsible for limb girdle muscular dystrophy 1F (LGMD1F) is one heterozygous single nucleotide deletion in the stop codon of the nuclear import factor Transportin 3 gene (TNPO3). This mutation causes a carboxy-terminal extension of 15 amino acids, producing a protein of unknown function (TNPO3_mut) that is co-expressed with wild-type TNPO3 (TNPO3_wt). TNPO3 has been involved in the nuclear transport of serine/arginine-rich proteins such as splicing factors and also in HIV-1 infection through interaction with the viral integrase and capsid. We analyzed the effect of TNPO3_mut on HIV-1 infection using PBMCs from patients with LGMD1F infected ex vivo. HIV-1 infection was drastically impaired in these cells and viral integration was reduced 16-fold. No significant effects on viral reverse transcription and episomal 2-LTR circles were observed suggesting that the integration of HIV-1 genome was restricted. This is the second genetic defect described after CCR5Δ32 that shows strong resistance against HIV-1 infection. |
| first_indexed | 2024-12-23T19:32:26Z |
| format | Article |
| id | doaj.art-4e773c58f83a4eb5b4da09a63b2f9f9d |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-23T19:32:26Z |
| publishDate | 2019-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-4e773c58f83a4eb5b4da09a63b2f9f9d2022-12-21T17:33:52ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-08-01158e100795810.1371/journal.ppat.1007958The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection.Sara Rodríguez-MoraFlore De WitJavier García-PerezMercedes BermejoMaría Rosa López-HuertasElena MateosPilar MartíSusana RochaLorena VigónFrauke ChristZeger DebyserJuan Jesús VílchezMayte CoirasJosé AlcamíThe causative mutation responsible for limb girdle muscular dystrophy 1F (LGMD1F) is one heterozygous single nucleotide deletion in the stop codon of the nuclear import factor Transportin 3 gene (TNPO3). This mutation causes a carboxy-terminal extension of 15 amino acids, producing a protein of unknown function (TNPO3_mut) that is co-expressed with wild-type TNPO3 (TNPO3_wt). TNPO3 has been involved in the nuclear transport of serine/arginine-rich proteins such as splicing factors and also in HIV-1 infection through interaction with the viral integrase and capsid. We analyzed the effect of TNPO3_mut on HIV-1 infection using PBMCs from patients with LGMD1F infected ex vivo. HIV-1 infection was drastically impaired in these cells and viral integration was reduced 16-fold. No significant effects on viral reverse transcription and episomal 2-LTR circles were observed suggesting that the integration of HIV-1 genome was restricted. This is the second genetic defect described after CCR5Δ32 that shows strong resistance against HIV-1 infection.https://doi.org/10.1371/journal.ppat.1007958 |
| spellingShingle | Sara Rodríguez-Mora Flore De Wit Javier García-Perez Mercedes Bermejo María Rosa López-Huertas Elena Mateos Pilar Martí Susana Rocha Lorena Vigón Frauke Christ Zeger Debyser Juan Jesús Vílchez Mayte Coiras José Alcamí The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection. PLoS Pathogens |
| title | The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection. |
| title_full | The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection. |
| title_fullStr | The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection. |
| title_full_unstemmed | The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection. |
| title_short | The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection. |
| title_sort | mutation of transportin 3 gene that causes limb girdle muscular dystrophy 1f induces protection against hiv 1 infection |
| url | https://doi.org/10.1371/journal.ppat.1007958 |
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