Sharon Bright Amanya, Brian Nyiro, Francis Waswa, Bonniface Obura, Rebecca Nakaziba, Eva Nabulime, Ashaba Fred Katabazi, Rose Nabatanzi, Alice Bayiyana, Gerald Mboowa, Alex Kayongo, Misaki Wayengera, Obondo J Sande
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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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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. 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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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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. 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引用次数: 1
摘要
背景:TRIM5α (Tripartite Motif Containing 5α， TRIM5α)是一种在人体细胞和组织中普遍存在的限制性因子，在HIV的免疫应答中起重要作用。TRIM5α靶向HIV衣壳破坏蛋白体。亲环蛋白A，一种细胞内蛋白也被报道以细胞特异性的方式影响HIV的感染性。因此，TRIM5α和亲环蛋白A基因的变异已被证明影响HIV-1疾病的进展。然而，这些变异并没有在乌干达的精英控制者中被记录下来，它们是否在病毒抑制中发挥作用在很大程度上仍然没有记录。我们的研究重点是在乌干达HIV-1精英控制者和非控制者中鉴定TRIM5α和亲环蛋白A基因的变异。结果:从序列分析来看，TRIM5α 2外显子rs10838525 G > A突变仅在精英控制者(30%)中发现，而在非控制者(25%)中发现5'UTR上的rs3824949突变。在亲环蛋白A启动子中，rs6850存在于62.5%的非控制者中，仅存在于10%的精英控制者中。此外，Cyclophillin A启动子中的rs17860048在精英控制者(30%)和非控制者(12.5%)中主要存在。从基因表达分析中，我们注意到，在精英对照中，各自的基因普遍升高，但这种差异没有统计学意义(TRIM5α p = 0.6095;亲环蛋白A p = 0.6389)。结论:TRIM5α和Cyclophillin 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精英控制者的病毒抑制。环亲素A基因中的rs6850可能是HIV-1在非控制者中快速进展的原因。应该对这些snp进行机制研究，以确定它们在HIV-1病毒抑制中的确切作用。
Variations in Trim5α and Cyclophilin A genes among HIV-1 elite controllers and non controllers in Uganda: a laboratory-based cross-sectional study.
Background: 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.
Results: 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).
Conclusion: 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.
期刊介绍：
Retrovirology is an open access, online journal that publishes stringently peer-reviewed, high-impact articles on host-pathogen interactions, fundamental mechanisms of replication, immune defenses, animal models, and clinical science relating to retroviruses. Retroviruses are pleiotropically found in animals. Well-described examples include avian, murine and primate retroviruses.
Two human retroviruses are especially important pathogens. These are the human immunodeficiency virus, HIV, and the human T-cell leukemia virus, HTLV. HIV causes AIDS while HTLV-1 is the etiological agent for adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. Retrovirology aims to cover comprehensively all aspects of human and animal retrovirus research.
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