IRF5‐TNOP3 polymorphisms are associated with elite control of HIV infection: A retrospective study

Author:

Sepúlveda‐Crespo Daniel12,Jiménez‐Sousa María A.12,Fernández‐Rodíguez Amanda12ORCID,Muñoz‐Fernández María A.345ORCID,Jiménez José Luis56,Moreno Santiago27,Garcia Felipe8,Martínez Isidoro12,Benito José M.910,Rallón Norma910,Resino Salvador12ORCID

Affiliation:

1. Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología (CNM) Instituto de Salud Carlos III (ISCIII) Madrid Spain

2. Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC) Instituto de Salud Carlos III Madrid Spain

3. Servicio de Inmunología, Laboratorio InmunoBiología Molecular Hospital General Universitario Gregorio Marañón Madrid Spain

4. Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER‐BBN) Instituto de Salud Carlos III Madrid Spain

5. Fundación para la Investigación Biomédica, Hospital General Universitario Gregorio Marañón Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM) Madrid Spain

6. Plataforma de Laboratorio Hospital General Universitario “Gregorio Marañón” Madrid Spain

7. Servicio de Enfermedades Infecciosas Hospital Universitario Ramón y Cajal Madrid Spain

8. Servicio de Enfermedades Infecciosas Hospital Clínic Barcelona Spain

9. HIV and Viral Hepatitis Research Laboratory, Instituto de Investigación Sanitaria Fundación Jiménez Díaz Universidad Autónoma de Madrid (IIS‐FJD, UAM) Madrid Spain

10. Hospital Universitario Rey Juan Carlos Móstoles Spain

Abstract

AbstractIRF5–TNPO3 polymorphisms have previously been related to immune response, and TNPO3 plays a role in human immunodeficiency virus (HIV)‐1 infection after nuclear import. Therefore, we analyzed the genetic association between IRF5–TNPO3 polymorphisms and the HIV elite control in long‐term nonprogressors (LTNPs). We performed a retrospective cohort study on 183 LTNPs, who were antiretroviral therapy‐naïve with CD4+ ≥ 500 cells/mm3, viral load ≤10 000 copies/mL, and asymptomatic over 10 years after HIV seroconversion. The primary outcome variable was HIV elite control (undetectable viral load in at least 90% of the measurements for at least 1 year). Seven IRF5–TNPO3 polymorphisms were genotyped using Agena Bioscience's MassARRAY platform. We found a significant association between specific IRF5–TNPO3 genotypes and HIV elite control: rs2004640 TT (aOR = 2.05; p = 0.041), rs10954213 AA (aOR = 1.95; p = 0.035), rs2280714 TT (aOR = 2.02; p = 0.031), and rs10279821 CC (aOR = 2.12; p = 0.017). We also found a significant association between IRF5‐TNPO3 haplotype TATC composed of the favorable significant polymorphisms (rs2004640, rs10954213, rs2280714, and rs10279821) and the HIV elite control (aOR = 1.59; p = 0.048). IRF5–TNPO3 rs2004640, rs10954213, rs2280714, and rs10279821 polymorphisms were related to HIV elite control in LTNPs. Our data provide new knowledge about the impact of IRF5–TNPO3 polymorphisms on HIV pathogenesis to understand the phenomenon of natural HIV control.

Funder

Ministerio de Ciencia e Innovación

Instituto de Salud Carlos III

Publisher

Wiley

Subject

Infectious Diseases,Virology

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