Mogensen Trine H
Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Clin Microbiol Infect. 2022 Nov;28(11):1411-1416. doi: 10.1016/j.cmi.2022.02.023. Epub 2022 Feb 24.
During the past decades, studies on patients with severe viral infections have revealed rare inborn errors of immunity (IEIs) underlying these diseases. This has led to important new insights into the molecular genetics and immunological mechanisms governing susceptibility to viral infection in humans.
Herein, the current knowledge on major IEIs predisposing to severe or chronic viral infections are described and discussed, and the clinical implications of these findings for individualized prophylaxis and treatment are outlined.
The review is based on a broad literature search, including relevant studies primarily based on patients, supported by experimental molecular models in vitro or in mice, to characterize the pathophysiological mechanism governing these disease conditions.
Current concepts and principles of genetic predisposition to viral infections in humans are described with a major focus on defects related to innate immune responses and new concepts of constitutive immune mechanisms. The topic therefore spans from seminal studies on the human genetics of herpesvirus infections in the central nervous system, severe influenza, and disease after vaccination with live attenuated viral vaccines, to genetic resistance to viral infection.
Past and present studies of patients with IEIs conferring vulnerability to viral infections have taught us important lessons on protective innate and adaptive antiviral immunity in humans. Such knowledge also has important clinical implications, allowing development of prophylactic and therapeutic solutions to prevent or dampen the clinical consequences of insufficient or dysregulated antiviral immunity in patients. Collectively, such measures are likely to improve patient management at an individualized level and help societies reduce the disease burden from viral infections.
在过去几十年中，对严重病毒感染患者的研究揭示了这些疾病背后罕见的先天性免疫缺陷（IEIs）。这为人类易患病毒感染的分子遗传学和免疫机制带来了重要的新见解。
本文描述并讨论了导致严重或慢性病毒感染的主要IEIs的现有知识，并概述了这些发现对个体化预防和治疗的临床意义。
本综述基于广泛的文献检索，包括主要基于患者的相关研究，并得到体外或小鼠实验分子模型的支持，以阐明这些疾病状态的病理生理机制。
描述了人类病毒感染遗传易感性的当前概念和原理，主要关注与先天免疫反应相关的缺陷以及组成性免疫机制的新概念。因此，该主题涵盖了从对中枢神经系统疱疹病毒感染、严重流感以及减毒活病毒疫苗接种后疾病的人类遗传学的开创性研究，到对病毒感染的遗传抗性。
过去和现在对易患病毒感染的IEIs患者的研究，让我们对人类保护性先天和适应性抗病毒免疫有了重要认识。这些知识也具有重要的临床意义，有助于开发预防和治疗方案，以预防或减轻患者抗病毒免疫不足或失调的临床后果。总体而言，这些措施可能会改善个体化水平的患者管理，并帮助社会减轻病毒感染的疾病负担。
