Faculty of Health Sciences, Lira University, Lira, Uganda.
Department of Immunology and Molecular Biology, Makerere University College of Health Sciences, Kampala, Uganda.
Retrovirology. 2020 Jul 6;17(1):19. doi: 10.1186/s12977-020-00527-z.
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.
三部分包含 5α（TRIM5α），一种在身体的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 靶向 HIV 衣壳进行蛋白酶体破坏。细胞内蛋白亲环素 A 也已被报道以细胞特异性方式影响 HIV 感染性。相应地，TRIM5α 和 Cyclophilin A 基因的变异已被记录下来，影响 HIV-1 疾病的进展。然而，在乌干达的精英控制器中，这些变异尚未被记录下来，它们在病毒抑制中是否起作用在很大程度上仍未被记录下来。我们的研究集中在鉴定乌干达 HIV-1 精英控制器和非控制器中 TRIM5α 和 Cyclophilin A 基因的变异。
从序列分析来看，TRIM5α 外显子 2 中的 rs10838525 G > A 突变仅在精英控制器（30%）中发现，而 5'UTR 中的 rs3824949 则在 25%的非控制器中发现。在 Cyclophilin A 启动子中，rs6850 见于 62.5%的非控制器中，仅见于 10%的精英控制器中。此外，Cyclophilin A 启动子中的 rs17860048 主要见于精英控制器（30%）和 12.5%的非控制器。从基因表达分析来看，我们注意到各自的基因在精英控制器中通常升高，但这一差异没有统计学意义（TRIM5α p = 0.6095；Cyclophilin A p = 0.6389）。
TRIM5α 和 Cyclophilin A 启动子的变异可能影响 HIV 病毒的抑制。TRIM5α 中的 rs10838525 SNP 可能有助于 HIV-1 精英控制器中的病毒抑制。Cyclophilin A 基因中的 rs6850 可能导致 HIV-1 非控制器中 HIV-1 的快速进展。这些 SNP 应通过机制进行研究，以确定它们在 HIV-1 病毒抑制中的精确作用。
