Division of Infection and Immunity/Systems Immunity University Research Institute, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK.
MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DS, UK.
Mucosal Immunol. 2021 Jan;14(1):14-25. doi: 10.1038/s41385-020-00355-6. Epub 2020 Nov 12.
Infection with respiratory viruses such as influenza, respiratory syncytial virus and coronavirus provides a difficult immunological challenge for the host, where a balance must be established between controlling viral replication and limiting damage to the delicate lung structure. Although the genetic architecture of host responses to respiratory viral infections is not yet understood, it is clear there is underlying heritability that influences pathogenesis. Immune control of virus replication is essential in respiratory infections, but overt activation can enhance inflammation and disease severity. Cytokines initiate antiviral immune responses but are implicated in viral pathogenesis. Here, we discuss how host genetic variation may influence cytokine responses to respiratory viral infections and, based on our current understanding of the role that cytokines play in viral pathogenesis, how this may influence disease severity. We also discuss how induced pluripotent stem cells may be utilised to probe the mechanistic implications of allelic variation in genes in virus-induced inflammatory responses. Ultimately, this could help to design better immune modulators, stratify high risk patients and tailor anti-inflammatory treatments, potentially expanding the ability to treat respiratory virus outbreaks in the future.
感染流感、呼吸道合胞病毒和冠状病毒等呼吸道病毒会给宿主带来严峻的免疫挑战，宿主必须在控制病毒复制和限制对脆弱肺部结构的损害之间取得平衡。尽管宿主对呼吸道病毒感染的反应的遗传结构尚未可知，但有潜在的遗传性会影响发病机制。免疫控制病毒复制对于呼吸道感染至关重要，但过度激活会加重炎症和疾病严重程度。细胞因子启动抗病毒免疫反应，但与病毒发病机制有关。在这里，我们讨论宿主遗传变异如何影响细胞因子对呼吸道病毒感染的反应，以及基于我们目前对细胞因子在病毒发病机制中的作用的理解，这可能如何影响疾病严重程度。我们还讨论了诱导多能干细胞如何用于探究基因中等位基因变异在病毒诱导的炎症反应中的机制意义。最终，这有助于设计更好的免疫调节剂，对高危患者进行分层，并针对炎症进行治疗，有可能扩大未来治疗呼吸道病毒爆发的能力。
