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

• Published in: Journal of medical virology 2023-06, Vol.95 (6), p.e28841-n/a
• Main Authors: Sepúlveda‐Crespo, Daniel, Jiménez‐Sousa, María A., Fernández‐Rodíguez, Amanda, Muñoz‐Fernández, María A., Jiménez, José Luis, Moreno, Santiago, Garcia, Felipe, Martínez, Isidoro, Benito, José M., Rallón, Norma, Resino, Salvador
• Format: Article
• Language: English
• Subjects: Antiretroviral agents; Antiretroviral therapy; beta Karyopherins - genetics; CD4 antigen; Genetic Predisposition to Disease; Genotype; Genotypes; Haplotypes; HIV; HIV elite controllers; HIV Infections; Human immunodeficiency virus; Humans; Immune response; Immune system; interferon regulatory factor 5; Interferon Regulatory Factors - genetics; LTNPs; Nuclear transport; Pathogenesis; Polymorphism, Single Nucleotide; Retrospective Studies; Seroconversion; single‐nucleotide polymorphisms; transportin 3; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.28841

IRF5–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.