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Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study
Retrovirology ( IF 2.7 ) Pub Date : 2020-07-06 , DOI: 10.1186/s12977-020-00527-z
Sharon Bright Amanya 1, 2 , Brian Nyiro 2 , Francis Waswa 2 , Bonniface Obura 1 , Rebecca Nakaziba 1 , Eva Nabulime 3 , Ashaba Fred Katabazi 2 , Rose Nabatanzi 2 , Alice Bayiyana 2 , Gerald Mboowa 2, 4 , Alex Kayongo 5 , Misaki Wayengera 2 , Obondo J Sande 2
Affiliation  

Tripartite Motif Containing 5 alpha (TRIM5α), a restriction factor produced ubiquitously in cells and tissues of the body plays an important role in the immune response against HIV. TRIM5α targets the HIV capsid for proteosomal destruction. Cyclophilin A, an intracellular protein has also been reported to influence HIV infectivity in a cell-specific manner. Accordingly, variations in TRIM5α and Cyclophilin A genes have been documented to influence HIV-1 disease progression. However, these variations have not been documented among Elite controllers in Uganda and whether they play a role in viral suppression remains largely undocumented. Our study focused on identifying the variations in TRIM5α and Cyclophilin A genes among HIV-1 Elite controllers and non-controllers in Uganda. From the sequence analysis, the rs10838525 G > A mutation in exon 2 of TRIM5α was only found among elite controllers (30%) while the rs3824949 in the 5′UTR was seen among 25% of the non-controllers. In the Cyclophilin A promoter, rs6850 was seen among 62.5% of the non-controllers and only among 10% elite controllers. Furthermore, rs17860048 in the Cyclophillin A promoter was predominantly seen among elite controllers (30%) and 12.5% non-controllers. From gene expression analysis, we noted that the respective genes were generally elevated among elite controllers, however, this difference was not statistically significant (TRIM5α p = 0.6095; Cyclophilin A p = 0.6389). Variations in TRIM5α and Cyclophillin A promoter may influence HIV viral suppression. The rs10838525 SNP in TRIM5α may contribute to viral suppression among HIV-1 elite controllers. The rs6850 in the cyclophillin A gene may be responsible for HIV-1 rapid progression among HIV-1 non-controllers. These SNPs should be investigated mechanistically to determine their precise role in HIV-1 viral suppression.

中文翻译:

乌干达 HIV-1 精英控制者和非控制者中 Trim5α 和亲环蛋白 A 基因的变化:一项基于实验室的横断面研究

含有 5 α (TRIM5α) 的三联基序是一种在人体细胞和组织中普遍产生的限制因子,在针对 HIV 的免疫反应中起着重要作用。TRIM5α 以 HIV 衣壳为目标进行蛋白体破坏。据报道,亲环蛋白 A 是一种细胞内蛋白,它以细胞特异性方式影响 HIV 感染性。因此,已证明 TRIM5α 和亲环蛋白 A 基因的变异会影响 HIV-1 疾病的进展。然而,乌干达的 Elite 控制者并未记录这些变异,而且它们是否在病毒抑制中发挥作用在很大程度上仍未记录。我们的研究重点是确定乌干达 HIV-1 精英控制者和非控制者之间 TRIM5α 和亲环蛋白 A 基因的变异。从序列分析,rs10838525 G > 仅在精英控制者 (30%) 中发现了 TRIM5α 外显子 2 的突变,而在 25% 的非控制者中发现了 5'UTR 中的 rs3824949。在 Cyclophilin A 启动子中,rs6850 出现在 62.5% 的非控制者中,仅出现在 10% 的精英控制者中。此外,亲环蛋白 A 启动子中的 rs17860048 主要出现在精英控制者 (30%) 和 12.5% 的非控制者中。从基因表达分析中,我们注意到各个基因在精英控制者中普遍升高,然而,这种差异在统计学上不显着(TRIM5α p = 0.6095;亲环蛋白 A p = 0.6389)。TRIM5α 和亲环蛋白 A 启动子的变异可能影响 HIV 病毒抑制。TRIM5α 中的 rs10838525 SNP 可能有助于抑制 HIV-1 精英控制者的病毒。亲环蛋白 A 基因中的 rs6850 可能是 HIV-1 非控制者中 HIV-1 快速进展的原因。应对这些 SNP 进行机械研究以确定它们在 HIV-1 病毒抑制中的确切作用。
更新日期:2020-07-06
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