1. The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection.
- Author
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Rodríguez-Mora S, De Wit F, García-Perez J, Bermejo M, López-Huertas MR, Mateos E, Martí P, Rocha S, Vigón L, Christ F, Debyser Z, Vílchez JJ, Coiras M, and Alcamí J
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, Female, HIV Infections genetics, HIV Infections virology, Humans, Infant, Male, Middle Aged, Muscular Dystrophies, Limb-Girdle genetics, Pedigree, Young Adult, HIV Infections prevention & control, HIV-1 physiology, Muscular Dystrophies, Limb-Girdle pathology, Mutation, Virus Replication genetics, beta Karyopherins genetics
- Abstract
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., Competing Interests: The authors have declared that no competing interest exist.
- Published
- 2019
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