2. Academic Validation
  3. The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection

The mutation of Transportin 3 gene that causes limb girdle muscular dystrophy 1F induces protection against HIV-1 infection

  • PLoS Pathog. 2019 Aug 29;15(8):e1007958. doi: 10.1371/journal.ppat.1007958.
Sara Rodríguez-Mora 1,  Flore De Wit 2,  Javier García-Perez 1,  Mercedes Bermejo 1,  María Rosa López-Huertas 1 3,  Elena Mateos 1,  Pilar Martí 4,  Susana Rocha 5,  Lorena Vigón 1,  Frauke Christ 2,  Zeger Debyser 2,  Juan Jesús Vílchez 4 6,  Mayte Coiras 1,  José Alcamí 1 7
Affiliations

Affiliations

  • 1 AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
  • 2 Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Flanders, Belgium.
  • 3 Department of Infectious Diseases, Hospital Ramón y Cajal, Alcalá de Henares University, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
  • 4 Neuromuscular Diseases Unit, Neurology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
  • 5 Laboratory for Photochemistry and Spectroscopy, Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Flanders, Belgium.
  • 6 Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
  • 7 Infectious Diseases Unit, IBIDAPS, Hospital Clínic, University of Barcelona, Spain.
PMID: 31465518 DOI: 10.1371/journal.ppat.1007958
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.

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