HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Africa Health Research Institute (AHRI), Durban, South Africa.
Front Immunol. 2021 May 5;12:669241. doi: 10.3389/fimmu.2021.669241. eCollection 2021.
HIV-1 must overcome host antiviral restriction factors for efficient replication. We hypothesized that elevated levels of bone marrow stromal cell antigen 2 (), a potent host restriction factor that interferes with HIV-1 particle release in some human cells and is antagonized by the viral protein Vpu, may associate with viral control. Using cryopreserved samples, from HIV-1 seronegative and seropositive Black women, we measured expression levels of mRNA using a real-time PCR assay and protein levels were validated by Western blotting. The expression level of showed an association with viral control within two independent cohorts of Black HIV infected females (r=-0.53, p=0.015, [n =21]; and r=-0.62, p=0.0006, [n=28]). DNA methylation was identified as a mechanism regulating levels, where increased methylation results in lower expression levels and associates with worse HIV disease outcome. We further demonstrate the ability to regulate levels using a DNA hypomethylation drug. Our results suggest as a factor for potential therapeutic intervention against HIV and other diseases known to involve .
HIV-1 必须克服宿主抗病毒限制因子才能进行有效的复制。我们假设，骨髓基质细胞抗原 2（）水平升高，作为一种有效的宿主限制因子，在某些人类细胞中干扰 HIV-1 颗粒的释放，并被病毒蛋白 Vpu 拮抗，可能与病毒控制有关。我们使用冷冻保存的样本，来自 HIV-1 血清阴性和阳性的黑人女性，使用实时 PCR 检测法测量了 mRNA 的表达水平，并通过 Western blot 验证了蛋白水平。在两个独立的黑人 HIV 感染女性队列中， 的表达水平与病毒控制呈负相关（r=-0.53，p=0.015，[n=21]；r=-0.62，p=0.0006，[n=28]）。DNA 甲基化被确定为调节 水平的机制，其中 甲基化增加导致表达水平降低，并与 HIV 疾病结局恶化相关。我们进一步证明了使用 DNA 低甲基化药物调节 水平的能力。我们的研究结果表明， 是针对 HIV 及其他已知涉及 的疾病进行潜在治疗干预的一个因素。
