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.

流感、呼吸道合胞病毒和冠状病毒等呼吸道病毒的感染给宿主带来了艰难的免疫挑战，必须在控制病毒复制和限制对脆弱肺部结构的损害之间建立平衡。尽管宿主对呼吸道病毒感染反应的遗传结构尚不清楚，但很明显存在影响发病机制的潜在遗传性。病毒复制的免疫控制对于呼吸道感染至关重要，但明显的激活会加剧炎症和疾病的严重程度。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，以及根据我们目前对细胞因子在病毒发病机制中所起作用的理解，这如何影响疾病的严重程度。我们还讨论了如何利用诱导多能干细胞来探讨病毒诱导的炎症反应中基因等位基因变异的机制意义。最终，这可能有助于设计更好的免疫调节剂，对高危患者进行分层并定制抗炎治疗，从而有可能扩大未来治疗呼吸道病毒爆发的能力。