Department of Cardiology and Pneumology, Charité Centrum 11 (Cardiovascular Medicine), Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
Basic Res Cardiol. 2013 Sep;108(5):372. doi: 10.1007/s00395-013-0372-y. Epub 2013 Aug 11.
Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.
最近的研究在心肌病和心脏移植患者的心脏中检测到了红病毒基因组。评估病毒的功能状态可能会提供超出病毒基因组检测的临床重要信息。在这里，我们报告称，在一组特定的心肌病患者中，红病毒的转录激活与心肌基因表达的明显改变有关。对 415 例连续的、临床疑似心肌病且心脏红病毒（B19V）阳性的患者进行了心内膜心肌活检（EMB），以筛查病毒编码的 VP1/VP2mRNA，该 mRNA 表示病毒的转录激活，并与转录活性与潜伏感染以及无病毒对照心脏中的心脏宿主基因表达模式相关联。仅在 415 例携带红病毒的患者中的 66/415 例（15.9%）的基线活检中检测到转录活性。在分子水平上，通过 EMB 的表达谱分析，揭示了 B19V 阳性患者与转录活性与潜伏病毒之间的显著差异。重要的是，潜伏 B19V 感染与对照组无法区分。涉及的基因编码抗病毒免疫反应、B19V 受体复合物和线粒体能量代谢的蛋白质。因此，红病毒的功能图谱允许定义一组以病毒编码的 VP1/VP2 转录本和异常的心脏心肌转录组为特征的 B19V 感染的心肌病患者亚组。正如这里首次报道的那样，潜伏 B19V 的重新激活是红病毒在一组心肌病患者中诱导改变的心脏基因表达的关键因素。病毒基因组检测不足以评估致病潜力，但应将额外的转录图谱纳入未来的发病机制和治疗研究中，包括心脏病学和移植医学。
