Viruses elicit long-term adaptive responses in the tissues they infect. Understanding viral adaptions in humans is difficult in organs such as the heart, where primary infected material is not routinely collected. In search of asymptomatic infections with accompanying host adaptions, we mined for cardio-pathogenic viruses in the unaligned reads of nearly 1000 human hearts profiled by RNA sequencing. Among virus-positive cases (~20%), we identified three robust adaptions in the host transcriptome related to inflammatory nuclear factor κB (NF-κB) signaling and posttranscriptional regulation by the p38-MK2 pathway. The adaptions are not determined by the infecting virus, and they recur in infections of human or animal hearts and cultured cardiomyocytes. Adaptions switch states when NF-κB or p38-MK2 is perturbed in cells engineered for chronic infection by the cardio-pathogenic virus, coxsackievirus B3. Stratifying viral responses into reversible adaptions adds a targetable systems-level simplification for infections of the heart and perhaps other organs.

中文翻译：

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心脏病毒适应的三种模式


病毒在它们感染的组织中引发长期的适应性反应。在心脏等器官中，了解人类的病毒适应是困难的，因为这些器官不会定期收集原发性感染物质。为了寻找伴有宿主适应的无症状感染，我们在通过 RNA 测序分析的近 1000 个人类心脏的未对齐读数中挖掘了心脏致病性病毒。在病毒阳性病例 （~20%） 中，我们在宿主转录组中确定了三个与炎症核因子 κB （NF-κB） 信号传导和 p38-MK2 通路的转录后调控相关的强健适应。适应不是由感染病毒决定的，它们在人或动物心脏和培养的心肌细胞感染中复发。当 NF-κB 或 p38-MK2 在为心脏致病病毒柯萨奇病毒 B3 慢性感染而设计的细胞中受到干扰时，适应会切换状态。将病毒反应分层为可逆适应，为心脏和其他器官感染增加了可靶向的系统级简化。