Institute of Medical Virology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Institute of Medical Virology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Trends Microbiol. 2021 Nov;29(11):973-982. doi: 10.1016/j.tim.2021.03.001. Epub 2021 Mar 20.
Pandemics are caused by novel pathogens to which pre-existing antibody immunity is lacking. Under these circumstances, the body must rely on innate interferon-mediated defenses to limit pathogen replication and allow development of critical humoral protection. Here, we highlight studies on disease susceptibility during H1N1 influenza and COVID-19 (SARS-CoV-2) pandemics. An emerging concept is that genetic and non-genetic deficiencies in interferon system components lead to uncontrolled virus replication and severe illness in a subset of people. Intriguingly, new findings suggest that individuals with autoantibodies neutralizing the antiviral function of interferon are at increased risk of severe COVID-19. We discuss key questions surrounding how such autoantibodies develop and function, as well as the general implications of diagnosing interferon deficiencies for personalized therapies.
大流行是由缺乏预先存在的抗体免疫的新型病原体引起的。在这种情况下，身体必须依靠先天的干扰素介导的防御来限制病原体的复制，并允许关键的体液保护的发展。在这里，我们重点介绍了 H1N1 流感和 COVID-19（SARS-CoV-2）大流行期间疾病易感性的研究。一个新出现的概念是，干扰素系统成分的遗传和非遗传缺陷导致一部分人病毒复制失控和严重疾病。有趣的是，新的发现表明，中和干扰素抗病毒功能的自身抗体的个体患严重 COVID-19 的风险增加。我们讨论了围绕这些自身抗体如何发展和发挥作用的关键问题，以及诊断干扰素缺陷对个性化治疗的一般意义。
