Examining the levels of acetylation, DNA methylation and phosphorylation in HIV-1 positive and multidrug-resistant TB-HIV patients.
Examining the levels of acetylation, DNA methylation and phosphorylation in HIV-1 positive and multidrug-resistant TB-HIV patients.
复制标题
DOI：
10.1016/j.jgar.2020.09.023
复制
发表时间：
2020-10
影响因子：
4.6
通讯作者：
M. Marimani;Aijaz Ahmad;S. Stacey;A. Dusé
中科院分区：
文献类型：
--
作者：
M. Marimani;Aijaz Ahmad;S. Stacey;A. Dusé
目的在本研究中，我们通过评估健康、耐多药 (MDR) TB-HIV 共感染者和 HIV-1 阳性个体等三个不同组中 7 个候选基因的表达，研究表观遗传修饰对宿主基因功能的影响。方法 10 名接受 TB 和 HIV 治疗的 MDR TB 和 HIV-1 共感染患者以及由 10 名新诊断的 HIV-1 感染者组成的队列 是从夏洛特马克塞克约翰内斯堡学术医院的结核病和艾滋病毒诊所招募的。值得注意的是，HIV-1 阳性个体在招募和采血时并未接受抗逆转录病毒治疗 (ART)。第三组由 10 名未感染耐多药结核病或艾滋病毒的健康参与者组成，是从威特沃特斯兰德大学招募的。从所有三个队列中收集的血液样本均用于提取血浆、总RNA和基因组DNA。结果我们的数据表明，DNA甲基转移酶1（DNMT1）和十一个易位甲基胞嘧啶双加氧酶1（TET1）基因的表达在HIV-1阳性患者中显着增加，而在耐多药结核病-HIV共感染患者中最低。相比之下，组蛋白乙酰转移酶（HAT）、组蛋白脱乙酰酶（HDAC）、蛋白酪氨酸激酶（PtkA）和蛋白酪氨酸磷酸酶（PtpA）mRNA表达水平在HIV-1感染者中显着增强，而在健康个体中最低。相反，所有三个研究组之间的 Dicer 表达水平相当。 结论 这项研究得出的有希望的初步数据可能会用于产生能够中和 MDR TB-HIV 和 HIV-1 感染的新型疫苗和治疗化合物。
ObjectivesIn this study, we examined the impact of epigenetic modifications on host gene functioning by assessing the expression of seven candidate genes in three separate groups including healthy, multidrug-resistant (MDR) TB-HIV co-infected and HIV-1 positive individuals.MethodsTen patients with MDR TB and HIV-1 co-infection on TB and HIV therapy and a cohort comprised of 10 newly diagnosed individuals with HIV-1 infection were recruited from the TB and HIV clinics at the Charlotte Maxeke Johannesburg Academic Hospital. Notably, the HIV-1 positive individuals were not placed on antiretroviral therapy (ART) at the time of recruitment and blood collection. A third group consisting of 10 healthy participants without MDR TB or HIV infection was recruited from the University of the Witwatersrand. Blood samples collected from all three cohorts were employed for extraction of plasma, total RNA and genomic DNA.ResultsOur data indicated that the expression ofDNA methyltransferase 1(DNMT1) andTen-eleven translocation methylcytosine dioxygenase 1(TET1) genes was significantly increased in HIV-1 positive patients and was lowest in MDR TB-HIV co-infected patients. By contrast,histone acetyltransferase(HAT),histone deacetylase(HDAC),protein tyrosine kinase(PtkA) andprotein tyrosine phosphatase(PtpA) mRNA expression levels were substantially enhanced in HIV-1 infected and were lowest in healthy individuals. Conversely,Dicerexpression levels were comparable among all three study groups.ConclusionPromising preliminary data emanating from this investigation may potentially be used for generation of novel vaccines and therapeutic compounds capable of neutralising MDR TB-HIV and HIV-1 infection.