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编码 RLR 和 TLR3 的基因多态性与人类免疫缺陷病毒和巨细胞病毒合并感染患者的 CMV DNA 血症。

Polymorphisms in the genes encoding RLR and TLR3 and CMV DNAemia in subjects coinfected with human immunodeficiency virus and cytomegalovirus.

机构信息

Laboratory of Virology, Institute of Medical Biology, Polish Academy of Sciences, 106 Lodowa St, Lodz, 93-232, Poland.

Department of Infectious Diseases and Hepatology, Medical University of Lodz, Lodz, Poland.

出版信息

Arch Virol. 2024 Sep 27;169(10):211. doi: 10.1007/s00705-024-06114-3.

Abstract

Cytomegalovirus (CMV) is a pathogen that is common worldwide and is often present in individuals infected with human immunodeficiency virus (HIV). Pattern recognition receptors (PRRs) are host sensors that activate the immune response against infectious agents. However, it is unclear whether PRR single-nucleotide polymorphisms (SNPs) are associated with the occurrence of CMV DNAemia in subjects coinfected with HIV and CMV. HIV/CMV-coinfected patients with and without CMV DNAemia were recruited for this study. The DDX58 rs10813831 and IFIH1 (rs3747517 and rs1990760) polymorphisms were genotyped using the TaqMan Allelic Discrimination Assay, whereas the DDX58 rs12006123 and TLR3 (rs3775291 and rs3775296) SNPs were analyzed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. A mutation present in at least one allele of the DDX58 rs12006123 SNP occurred at least two times more frequently in HIV/CMV-coinfected patients with CMV DNAemia than in coinfected subjects without CMV DNAemia (OR, 2.50; 95% CI, 1.33-4.68; p = 0.004, in the dominant model). A higher level of CMV DNAemia was observed in subjects who had the heterozygous (GA) or homozygous recessive (AA) genotype for the DDX58 rs12006123 SNP compared with those who had the wild-type (GG) genotype (p = 0.0003). Moreover, in subjects with a mutation detected in at least one allele of the DDX58 rs12006123 SNP, a lower serum IFN-β concentration was found compared with those who had a wild-type (GG) genotype for this polymorphism (p = 0.024). The DDX58 rs12006123 SNP is associated with CMV DNAemia in HIV/CMV-coinfected patients.

摘要

巨细胞病毒 (CMV) 是一种在全球范围内普遍存在的病原体,通常存在于感染人类免疫缺陷病毒 (HIV) 的个体中。模式识别受体 (PRR) 是宿主传感器,可激活针对感染因子的免疫反应。然而,目前尚不清楚 PRR 单核苷酸多态性 (SNP) 是否与 HIV 和 CMV 合并感染患者 CMV DNAemia 的发生有关。本研究招募了 HIV/CMV 合并感染且有或无 CMV DNAemia 的患者。使用 TaqMan 等位基因鉴别分析检测 DDX58 rs10813831 和 IFIH1(rs3747517 和 rs1990760) 多态性,而 DDX58 rs12006123 和 TLR3(rs3775291 和 rs3775296) SNP 则通过聚合酶链反应限制片段长度多态性 (PCR-RFLP) 分析进行分析。DDX58 rs12006123 SNP 的至少一个等位基因中存在的突变在 HIV/CMV 合并感染且有 CMV DNAemia 的患者中至少出现两倍的频率,而在合并感染且无 CMV DNAemia 的患者中则不然(OR,2.50;95%CI,1.33-4.68;p=0.004,在显性模型中)。与野生型 (GG) 基因型相比,DDX58 rs12006123 SNP 杂合子 (GA) 或纯合子隐性 (AA) 基因型的患者中观察到更高水平的 CMV DNAemia (p=0.0003)。此外,在至少一个 DDX58 rs12006123 SNP 等位基因中检测到突变的患者中,与该多态性的野生型 (GG) 基因型相比,血清 IFN-β 浓度较低(p=0.024)。DDX58 rs12006123 SNP 与 HIV/CMV 合并感染患者的 CMV DNAemia 相关。

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