Next-generation sequencing of CCR5, CXCR4, and IFNAR1 variants in relation to HIV-1 disease progression and ART response

• Published in: Scientific reports Vol. 15; no. 1; pp. 26511 - 13
• Main Authors: Pekkoc-Uyanik, Kubra Cigdem, Todurga-Seven, Zeynep Gizem, Shahzadi, Andleeb, Sonmez, Haktan, Mercan, Sevcan, Mete, Bilgul, Tabak, Fehmi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.07.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 3' Untranslated regions; 5' Untranslated regions; 631/208; 631/250; 692/308; 692/4017; Acquired immune deficiency syndrome; Adult; AIDS; Annotations; Antiretroviral therapy; CC chemokine receptors; CCR5; CD4 antigen; CD4 Lymphocyte Count; Chemokines; CXCR4; CXCR4 protein; Disease; Disease Progression; Female; Genomes; Genotype; Genotypes; Genotyping; High-Throughput Nucleotide Sequencing; HIV; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - virology; HIV-1; Human immunodeficiency virus; Humanities and Social Sciences; Humans; IFNAR1; Immune system; Lymphocytes; Lymphocytes T; Male; Middle Aged; multidisciplinary; Next-generation sequencing; Polymophism; Polymorphism, Single Nucleotide; Receptor, Interferon alpha-beta - genetics; Receptors, CCR5 - genetics; Receptors, CXCR4 - genetics; Risk factors; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Software; Variation; Istanbul Turkey; United States > US; Turkey; Next-generation sequencing; HIV; Polymophism; Genetic variation; CXCR4; CCR5; IFNAR1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-11843-9

HIV, which causes acquired immune deficiency syndrome (AIDS), invades the host cell via the CD4 receptor and CCR5 or CXCR4 co-receptors. Interferons induced early in HIV infection induce an antiviral defense mechanism through IFNAR signaling. Our study aimed to examine the relationship between CCR5 , CXCR4 , and IFNAR1 gene variations as a risk factor in HIV + patients and their response to their clinical parameters. Targeted next-generation sequencing (tNGS) was used to perform molecular genotyping analysis of the CCR5 , CXCR4, and IFNAR1 genes in genomic DNA from 22 HIV + patients and 25 healthy individuals as controls. We detected 13 rare mutations in the study, including 3 missense, 1 synonymous, 2 5′UTR, 4 3′UTR, and 1 frameshift variation. We also analyzed 6 common variants in the IFNAR1 and CXCR4 genes. HIV + patients carrying the homozygous TT genotype of the IFNAR1 intronic rs2856973:T > A variant had higher CD4 + T cell counts compared with patients carrying the TA + AA genotypes of the rs2856973 variant in the naive and first month of the ART ( p  = 0.001 and p  = 0.001, respectively). Similarly, participants receiving ART with a TT genotype of rs2856973:T > A showed a significantly higher CD4 + T cell count in the third month ( p  = 0.001). Patients carrying the homozygous wild-type genotype of the CXCR4 intronic rs2680880:A > T SNP had lower CD4 + T cell count compared with subjects carrying the AT + TT mutant genotypes of rs2680880:A > T in the naive and first-month period ( p  = 0.015 and p  = 0.025, respectively). Our results demonstrate that intronic variations in the IFNAR1 rs2856973:T > A and CXCR4 rs2680880:A > T genes can contribute to modifications in HIV progression and CD4 + T recovery under ART.