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

Fecha de publicación: 01/08/2019

Autores de IIS La Fe

Juan Jesús Vílchez Padilla

Autor

Participantes ajenos a IIS La Fe

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
Coiras M
Alcamí J

Grupos

Patología Neuromuscular y Ataxias

Investigador Principal

Teresa Sevilla Mantecón

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 CCR5 32 that shows strong resistance against HIV-1 infection.

Datos de la publicación

ISSN/ISSNe:: 1553-7366, 1553-7374
Tipo:: Article
Páginas:: -
DOI:: 10.1371/journal.ppat.1007958
Factor de Impacto:: 3,640 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Rodríguez-Mora S:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
De Wit F:: Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Flanders, Belgium
García-Perez J:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Bermejo M:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
López-Huertas MR:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain

Department of Infectious Diseases, Hospital Ramón y Cajal, Alcalá de Henares University, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain
Mateos E:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Martí P:: Neuromuscular Diseases Unit, Neurology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
Rocha S:: Laboratory for Photochemistry and Spectroscopy, Molecular Imaging and Photonics, Department of Chemistry, KU Leuven, Flanders, Belgium
Vigón L:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Christ F:: Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Flanders, Belgium
Debyser Z:: Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Flanders, Belgium
Vílchez JJ:: Neuromuscular Diseases Unit, Neurology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain

Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain
Coiras M:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Alcamí J:: AIDS Immunopathogenesis Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain

Infectious Diseases Unit, IBIDAPS, Hospital Clínic, University of Barcelona, Spain