Division of Infection and Immunity/Systems Immunity University Research Institute, Cardiff, United Kingdom.
Front Immunol. 2019 Jan 29;10:78. doi: 10.3389/fimmu.2019.00078. eCollection 2019.
Human cytomegalovirus (HCMV) is a β-herpesvirus with high sero-prevalence within the human population. Primary HCMV infection and life-long carriage are typically asymptomatic. However, HCMV is implicated in exacerbation of chronic conditions and associated damage in individuals with intact immune systems. Furthermore, HCMV is a significant cause of morbidity and mortality in the immunologically immature and immune-compromised where disease is associated with tissue damage. Infection-induced inflammation, including robust cytokine responses, is a key component of pathologies associated with many viruses. Despite encoding a large number of immune-evasion genes, HCMV also triggers the induction of inflammatory cytokine responses during infection. Thus, understanding how cytokines contribute to CMV-induced pathologies and the mechanisms through which they are regulated may inform clinical management of disease. Herein, we discuss our current understanding based on clinical observation and modeling of disease of the role that cytokines play in CMV pathogenesis. Specifically, in the context of the different tissues and organs in which CMV replicates, we give a broad overview of the beneficial and adverse effects that cytokines have during infection and describe how cytokine-mediated tissue damage is regulated. We discuss the implications of findings derived from mice and humans for therapeutic intervention strategies and our understanding of how host genetics may influence the outcome of CMV infections.
人巨细胞病毒（HCMV）是一种β疱疹病毒，在人类中具有很高的血清流行率。原发性 HCMV 感染和终身携带通常无症状。然而，HCMV 与免疫系统健全的个体中慢性疾病的恶化和相关损害有关。此外，HCMV 是免疫不成熟和免疫功能低下个体发病时与组织损伤相关的发病率和死亡率的重要原因。感染诱导的炎症，包括强烈的细胞因子反应，是许多病毒相关病理学的一个关键组成部分。尽管 HCMV 编码了大量的免疫逃避基因，但在感染过程中也会触发炎症细胞因子反应的诱导。因此，了解细胞因子如何导致 CMV 诱导的病理学以及它们的调节机制可能为疾病的临床管理提供信息。在此，我们根据疾病的临床观察和建模来讨论我们目前对细胞因子在 CMV 发病机制中的作用的理解。具体而言，在 CMV 复制的不同组织和器官的背景下，我们广泛概述了细胞因子在感染过程中产生的有益和有害影响，并描述了细胞因子介导的组织损伤是如何被调节的。我们讨论了从老鼠和人类中得出的发现对治疗干预策略的影响，以及我们对宿主遗传学如何影响 CMV 感染结果的理解。
