Introduction: Since the identification of HIV, several studies reported the unusual case of small groups of subjects showing natural resistance to HIV infection. These subjects are referred to as HIV-1-exposed seronegative (HESN) individuals and include people located in different areas, with diverse ethnic backgrounds and routes of exposure. The mechanism/s responsible for protection from infection in HESN individuals are basically indefinite and most likely are multifactorial.Areas covered: Host factors, including genetic background as well as natural and acquired immunity, have all been associated with this phenomenon. Recently, epigenetic factors have been investigated as possible determinants of reduced susceptibility to HIV infection. With the advent of the OMICS era, the availability of techniques such as GWAS, RNAseq, and exome-sequencing in both bulk cell populations and single cells will likely lead to great strides in the understanding of the HESN mystery.Expert opinion: The employment of increasingly sophisticated techniques is allowing the gathering of enormous amounts of data. The integration of such information will provide important hints that could lead to the identification of viral and host correlates of protection against HIV infection, allowing the development of more effective preventative and therapeutic regimens.

中文翻译：

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对 HIV-1 感染的自然抵抗力的遗传和表观遗传调控：揭示 HESN 秘密的新方法。

简介：自从发现 HIV 以来，一些研究报告了一小群人对 HIV 感染表现出天然抵抗力的不寻常案例。这些受试者被称为 HIV-1 暴露的血清阴性 (HESN) 个体，包括位于不同地区、具有不同种族背景和暴露途径的人。负责保护 HESN 个体免受感染的机制基本上是不确定的，很可能是多因素的。涵盖的领域：宿主因素，包括遗传背景以及自然和获得性免疫，都与这种现象有关。最近，已将表观遗传因素作为降低 HIV 感染易感性的可能决定因素进行了研究。随着 OMICS 时代的到来，GWAS、RNAseq、大量细胞群和单细胞中的外显子组测序可能会在理解 HESN 之谜方面取得巨大进步。专家意见：越来越复杂的技术的使用允许收集大量数据。这些信息的整合将提供重要的提示，可能导致识别病毒和宿主对 HIV 感染的保护相关性，从而开发更有效的预防和治疗方案。