Obeagu Emmanuel Ifeanyi
Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe.
Ann Med Surg (Lond). 2025 Mar 7;87(6):3381-3387. doi: 10.1097/MS9.0000000000003142. eCollection 2025 Jun.
HIV infection in infants poses unique challenges due to the interplay between an immature immune system and the viral mechanisms that exploit it. Recent research has unveiled critical insights into how epigenetic modifications, such as DNA methylation, histone modifications, and noncoding RNA regulation, specifically influence immune responses in HIV-infected infants. These modifications are not merely passive markers of infection but active players in immune dysregulation, contributing to persistent immune activation and the skewing of T-cell differentiation. Emerging studies have highlighted that these epigenetic alterations may play a role in the heightened vulnerability of HIV-infected infants to opportunistic infections and their variable responses to antiretroviral therapy (ART). A growing body of evidence suggests that epigenetic changes in key immune regulatory genes are significantly different in HIV-infected infants compared to uninfected controls. These differences have been linked to altered expression of cytokines, impaired T-cell functionality, and chronic inflammation, which are pivotal in disease progression. Specifically, recent findings indicate that persistent DNA methylation changes in genes involved in T-cell exhaustion could be a major driver of the reduced efficacy of ART in some infants, potentially leading to long-term immune system impairment. Moreover, novel insights into how miRNAs modulate the immune environment in these infants suggest potential targets for therapeutic intervention, aiming to enhance immune recovery and reduce viral reservoirs.
由于未成熟免疫系统与利用该系统的病毒机制之间的相互作用，婴儿感染艾滋病毒带来了独特的挑战。最近的研究揭示了表观遗传修饰（如DNA甲基化、组蛋白修饰和非编码RNA调控）如何具体影响艾滋病毒感染婴儿的免疫反应的关键见解。这些修饰不仅是感染的被动标记，而且是免疫失调的积极参与者，导致持续的免疫激活和T细胞分化的偏差。新出现的研究强调，这些表观遗传改变可能在艾滋病毒感染婴儿对机会性感染的高度易感性及其对抗逆转录病毒疗法（ART）的不同反应中起作用。越来越多的证据表明，与未感染的对照组相比，艾滋病毒感染婴儿关键免疫调节基因的表观遗传变化显著不同。这些差异与细胞因子表达改变、T细胞功能受损和慢性炎症有关，而这些在疾病进展中至关重要。具体而言，最近的研究结果表明，参与T细胞耗竭的基因中持续的DNA甲基化变化可能是一些婴儿抗逆转录病毒疗法疗效降低的主要驱动因素，可能导致长期免疫系统损害。此外对微小RNA如何调节这些婴儿免疫环境的新见解提示了治疗干预的潜在靶点，旨在增强免疫恢复并减少病毒储存库。
