HIV-1库细胞选择的性别差异与先天免疫谱的改变有关

IF 14.6 1区 医学 Q1 CELL BIOLOGY
Toong Seng Tan, Ce Gao, Alexander S. Hochroth, Liliana Vela, Leah Carrere, Sruthi Kalavacherla, Seohyun Hong, Melanie Lancien, Chloe M. Naasz, Aischa Niesar, Samantha K. Marzi, Isabelle C. Roseto, Benjamin Bone, Xiaodong Lian, Yuko Yuki, Mathias Viard, Rebecca Hoh, Deborah K. McMahon, Ronald J. Bosch, Seble G. Kassaye, Rajesh T. Gandhi, Mary Carrington, Steven G. Deeks, Phyllis C. Tien, Michael J. Peluso, Jeffrey M. Jacobson, Mathias Lichterfeld, Xu G. Yu
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引用次数: 0

摘要

尽管抗逆转录病毒抑制剂治疗(ART), HIV-1仍持续存在,主要是因为被感染的记忆CD4 T细胞,即所谓的病毒库细胞,携带染色体整合的病毒DNA作为“前病毒”,抵抗人类免疫系统的清除。生物性别影响宿主免疫反应,并可能影响HIV-1库细胞在长期抗逆转录病毒治疗HIV感染过程中的选择和进化。我们通过单分子扩增评估了来自30名女性和35名男性HIV-1感染者的4073多个个体前病毒,这些患者接受抗逆转录病毒治疗的中位时间为20年。我们观察到,女性HIV-1储存库的特征是前病毒系统发育复杂性较低,克隆扩增的完整前病毒比例增加,以及整合到人类基因组抑制异染色质位置的完整前病毒比例较高。这种独特的病毒库在女性中的进化与先天免疫反应的改善有关,特别是NK细胞。相反,病毒序列适应适应性T细胞免疫应答的迹象在来自男性的完整HIV-1前病毒中更为明显。总的来说,这些数据表明,在抗逆转录病毒治疗期间,女性免疫系统驱动HIV-1库细胞免疫选择的能力更强,推测是因为先天免疫功能的改善。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sex differences in HIV-1 reservoir cell selection are linked to altered innate immune profiles
HIV-1 persistence despite suppressive antiretroviral therapy (ART) is primarily because of infected memory CD4 T cells, so-called viral reservoir cells, that harbor chromosomally integrated viral DNA as a “provirus” and resist clearance by the human immune system. Biological sex affects host immune responses and may influence selection and evolution of HIV-1 reservoir cells during long-term ART for HIV infection. We assessed more than 4073 individual proviruses through single-molecule amplification from 30 females and 35 males living with HIV-1 and treated with ART for a median of 20 years. We observed that the HIV-1 reservoir profile in females was characterized by lower proviral phylogenetic complexity, an increased proportion of clonally expanded intact proviruses, and a higher proportion of intact proviruses integrated into repressive heterochromatin locations of the human genome. The evolution of this distinct viral reservoir profile in females was associated with an improved signature of innate immune responses, specifically those of NK cells. On the contrary, signs of viral sequence adaptation to adaptive T cell immune responses were more pronounced in intact HIV-1 proviruses from males. Collectively, these data suggest a stronger ability of the female immune system to drive immune selection of HIV-1 reservoir cells during ART, putatively because of improved innate immune function.
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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