Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/8481
The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection
Rodriguez‑Mora, Sara ISCIII | De Wit, Flore | Garcia-Perez, Javier ISCIII | Bermejo, Mercedes ISCIII | Lopez-Huertas, Maria Rosa ISCIII | Mateos, Elena ISCIII | Marti, Pilar | Rocha, Susana CNIC | Vigon-Hernandez, Lorena ISCIII | Christ, Frauke | Debyser, Zeger | Vílchez, Juan Jesús | Coiras, Mayte ISCIII | Alcamí, José ISCIII
PLoS Pathog. 2019 Aug 29;15(8):e1007958
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.
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